Prosthetic valve for replacing mitral valve

ABSTRACT

A prosthetic apparatus for implantation in a native mitral valve includes a main body for placement within the native mitral annulus. The main body is compressible to a radially compressed state for delivery into the heart and is self-expandable from the compressed state to a radially expanded state for implantation. A valve structure is mounted within a lumen of the main body and preferably forms three leaflets made of pericardium. An atrial sealing member is disposed along an atrial portion of the main body and ventricular anchors are coupled to a ventricular portion of the main body. The atrial sealing member impedes the flow of blood between the main body and the native annulus. The ventricular anchors are positioned outside the main body for capturing native mitral valve leaflets between the main body and the ventricular anchors.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 15/227,238, filed Aug. 3, 2016, which is a continuation of U.S.patent application Ser. No. 14/801,713, filed Jul. 16, 2015, now U.S.Pat. No. 9,433,500, which is a continuation of U.S. patent applicationSer. No. 14/255,179, filed Apr. 17, 2014, now U.S. Pat. No. 9,084,676,which is a continuation of U.S. patent application Ser. No. 14/025,594,filed Sep. 12, 2013, now U.S. Pat. No. 8,926,691, which is acontinuation of U.S. patent application Ser. No. 13/597,122, filed Aug.28, 2012, now U.S. Pat. No. 8,585,755, which is a continuation of U.S.patent application Ser. No. 12/959,292, filed Dec. 2, 2010, now U.S.Pat. No. 8,449,599, which claims the benefit of U.S. ProvisionalApplication Nos. 61/287,099, filed Dec. 16, 2009, and 61/266,774, filedDec. 4, 2009, all of which are incorporated herein by reference.

FIELD

This disclosure pertains generally to prosthetic devices for repairingand/or replacing native heart valves, and in particular to prostheticvalves for replacing defective mitral valves, as well as methods anddevices for delivering and implanting the same within a human heart.

BACKGROUND

Prosthetic valves have been used for many years to treat cardiacvalvular disorders. The native heart valves (i.e., the aortic,pulmonary, tricuspid and mitral valves) serve critical functions inassuring the forward flow of an adequate supply of blood through thecardiovascular system. These heart valves can be rendered less effectiveby congenital malformations, inflammatory processes, infectiousconditions or disease. Such damage to the valves can result in seriouscardiovascular compromise or death. For many years the definitivetreatment for such disorders was the surgical repair or replacement ofthe valve during open heart surgery. However, such surgeries are highlyinvasive and are prone to many complications. Therefore, elderly andfrail patients with defective heart valves often go untreated. Morerecently a transvascular technique has been developed for introducingand implanting a prosthetic heart valve using a flexible catheter in amanner that is much less invasive than open heart surgery.

In this technique, a prosthetic valve is mounted in a crimped state onthe end portion of a flexible catheter and advanced through a bloodvessel of the patient until the valve reaches the implantation site. Thevalve at the catheter tip is then expanded to its functional size at thesite of the defective native valve such as by inflating a balloon onwhich the valve is mounted.

Another known technique for implanting a prosthetic aortic valve is atransapical approach where a small incision is made in the chest wall ofa patient and the catheter is advanced through the apex (i.e., bottomtip) of the heart. Transapical techniques are disclosed in U.S. PatentApplication Publication No. 2007/0112422, which is hereby incorporatedby reference. Like the transvascular approach, the transapical approachcan include a balloon catheter having a steering mechanism fordelivering a balloon-expandable prosthetic heart valve through anintroducer to the aortic annulus. The balloon catheter can include adeflecting segment just proximal to the distal balloon to facilitatepositioning of the prosthetic heart valve in the proper orientationwithin the aortic annulus.

The above techniques and others have provided numerous options for highoperative risk patients with aortic valve disease to avoid theconsequences of open heart surgery and cardiopulmonary bypass. Whiledevices and procedures for the aortic valve are well-developed, suchcatheter-based procedures are not necessarily applicable to the mitralvalve due to the distinct differences between the aortic and mitralvalve. The mitral valve has complex subvalvular apparatus, i.e., chordaetendinae, which are not present in the aortic valve.

Surgical mitral valve repair techniques (e.g., mitral annuloplasty) haveincreased in popularity due to their high success rates, and clinicalimprovements noted after repair. In addition to the existing mitralvalve repair technologies, there are a number of new technologies aimedat making mitral valve repair a less invasive procedure. Thesetechnologies range from iterations of the Alfieri stitch procedure tocoronary sinus-based modifications of mitral anatomy to subvalvularplications or ventricular remodeling devices, which would incidentallycorrect mitral regurgitation.

However, for mitral valve replacement, few less-invasive options areavailable. There are approximately 25,000 mitral valve replacements(MVR) each year in the United States. However, it is estimated that over300,000 patients who meet guidelines for treatment are denied treatmentbased on their age and/or co-morbidities. Thus, a need exists forminimally invasive techniques for replacing the mitral valve.

SUMMARY

Prosthetic mitral valves, components thereof, and methods and devicesfor implanting the same are described herein.

A prosthetic apparatus is described that is configured for implanting atthe native mitral valve region of the heart and includes a main bodythat is radially compressible to a radially compressed state andself-expandable from the compressed state to a radially expanded state.The prosthetic apparatus also comprises at least one ventricular anchorcoupled to the main body and disposed outside of the main body such thatwhen the main body is compressed to the compressed state, aleaflet-receiving space between the ventricular anchor and an outersurface of the main body increases to receive a native valve leaflettherebetween. When the main body self-expands to the expanded state inthe absence of any substantial external inward forces on the main bodyor the ventricular anchor, the space decreases to capture the leafletbetween the main body and the ventricular anchor.

In some embodiments, a prosthetic apparatus, for implanting at thenative mitral valve region of the heart, includes a frame having a mainbody and at least one ventricular anchor coupled to and disposed outsideof the main body. The prosthetic apparatus also includes a plurality ofleaflets supported by the main body that form a one-way valve for theflow of blood through the main body. The main body is radiallycompressible to a radially compressed state for delivery into the bodyand self-expandable from the compressed state to a radially expandedstate. The ventricular anchor comprises a base that is fixedly securedto the main body, a free end portion opposite the base, and anintermediate portion defining a leaflet-receiving space between theventricular anchor and the main body for receiving a leaflet of thenative valve. Expansion of the main body from its compressed state toits radially expanded state in the absence of any radial inward forceson the ventricular anchor causes the leaflet-receiving space todecrease.

In other embodiments, a prosthetic apparatus for implanting at thenative mitral valve region includes a main body, at least oneventricular anchor and at least one atrial anchor. The main body isconfigured for placement within the native mitral valve and iscompressible to a compressed state for delivery into the heart andself-expandable from the compressed state to an expanded state. At leastone ventricular anchor is coupled to and disposed outside of the mainbody such that, in the expanded state, a leaflet-receiving space existsbetween the ventricular anchor and an outer surface of the main body toreceive a free edge portion of a native valve leaflet. The ventricularanchor comprises an engagement portion configured to extend behind thereceived native leaflet and contact a ventricular surface of the nativemitral annulus, the annulus connection portion of the received nativeleaflet, or both the ventricular surface of the native annulus and theannulus connection portion of the received native leaflet. At least oneatrial sealing member is coupled to and disposed outside of the mainbody and is configured to contact an atrial portion of the native mitralannulus, the annulus connection portion of the received native leaflet,or both the atrial surface of the native annulus and the annulusconnection portion of the received native leaflet at a location oppositefrom the engagement portion of the ventricular anchor for retention ofthe prosthetic apparatus and/or prevention of paravalvular leakage.

Exemplary delivery systems are also described for delivering aprosthetic apparatus into the heart. Some embodiments include an innersheath having a distal end portion having at least one longitudinal slotextending proximally from a distal end of the inner sheath. The distalend portion of the inner sheath is configured to contain the prostheticapparatus in a radially compressed state. An outer sheath is positionedconcentrically around the inner sheath and at least one of the innersheath and outer sheath is movable axially relative to the other betweena first position in which the outer sheath extends over at least aportion of the longitudinal slot and a second position in which the atleast a portion of the longitudinal slot is uncovered by the outersheath so to allow a portion of the prosthetic apparatus containedwithin the inner sheath to expand radially outward through the slot.

Exemplary methods are also described for implanting a prostheticapparatus at the native mitral valve region of the heart. One suchmethod includes delivering the prosthetic apparatus into the heart in aradially compressed state; allowing a ventricular anchor to self-expandaway from a main body of the frame while the main body is held in thecompressed state, thereby increasing a gap between the ventricularanchor and an outer surface of the main body; positioning the main bodyin the annulus of the native mitral valve and the ventricular anchoradjacent the ventricular side of a native mitral valve leaflet such thatthe leaflet is disposed in the gap between the ventricular anchor andthe outer surface of the main body; and allowing the main body toself-expand to an expanded state such that the gap decreases to capturethe leaflet between the outer surface of the main body and theventricular anchor.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross sectional view of the human heart.

FIG. 2 is another cross sectional view of the human heart showing themitral valve region.

FIG. 3 is a schematic view of the native mitral valve anatomy showingthe mitral leaflets attached to the papillary muscles via chordaetendineae.

FIG. 4A is a diagram of native mitral valve showing Carpentiernomenclature.

FIG. 4B shows a native mitral valve with a gap between the leaflets.

FIGS. 4C and 4D show an exemplary prosthetic valve positioned within anative mitral valve.

FIG. 5 is a side view of an exemplary embodiment of a prosthetic valve.

FIG. 6 shows the prosthetic valve of FIG. 5 rotated 90 degrees withrespect to a longitudinal axis of the value.

FIG. 7 is a ventricular (outflow) view of the prosthetic valve shown ofFIG. 5.

FIGS. 8-10 are views corresponding to FIGS. 5-7, showing an exemplaryembodiment of a frame of the prosthetic valve of FIGS. 5-7.

FIGS. 11-16 are a series of side views of the frame of FIG. 9, withoutthe atrial sealing member, showing the leaflet-receiving spaces betweenthe ventricular anchors and the main body increasing as the main body isradially compressed.

FIGS. 17-22 are a series of end views corresponding to FIGS. 11-16,respectively.

FIG. 23 is a cross-sectional view of the heart showing the frame of FIG.9 implanted in the mitral valve region, wherein the native mitral valveleaflets are captured between the main body and the ventricular anchors.

FIG. 24 shows exemplary dimensions of the atrial sealing member, mainbody and ventricular anchors of FIG. 9.

FIG. 25 shows an exemplary embodiment of a frame, with the atrialsealing member excluded, comprising a “T” shaped pushing memberextending downward from a ventricular end of the main body.

FIG. 26 shows an exemplary embodiment of a frame, with the atrialsealing member excluded, comprising a “V” shaped pushing memberextending downward from the ventricular end of the main body.

FIGS. 27-29 show an exemplary embodiment of a prosthetic valve having aframe with four ventricular anchors.

FIGS. 30-32 show the frame of the prosthetic valve shown in FIGS. 27-29.

FIG. 33 is a cross-sectional view of the heart showing the frame ofFIGS. 30-32 implanted in the mitral valve region.

FIG. 34 is a cross-sectional view of the heart showing an embodiment ofa frame, comprising extended ventricular anchors and an atrial sealingmember, implanted in the mitral valve region such that the mitralannulus and/or native leaflets are compressed between the ends of theextended ventricular anchors and the atrial sealing member.

FIGS. 35 and 36 are side views of an exemplary embodiment of a framecomprising “S” shaped ventricular anchors.

FIGS. 37 and 38 are side and top views, respectively, of an exemplaryembodiment of a frame, with the atrial sealing member excluded,comprising wider shaped ventricular anchors.

FIG. 39 is a cross-sectional view of the heart showing an embodiment ofa frame implanted in the mitral valve region, wherein the ventricularanchors remain separated from the body of the frame after expansion andthe ventricular anchors contact the lower ends of the mitral leaflets toutilize tension from the chordae tendineae to retain the frame.

FIG. 40 shows an exemplary embodiment of a frame comprising asubstantially flat atrial sealing member.

FIG. 41 shows an exemplary embodiment of a frame comprising an upwardlyextending atrial sealing member.

FIG. 42 shows an exemplary embodiment of a frame comprising an upwardlyextending atrial sealing member and extended ventricular anchors.

FIG. 43 shows an exemplary embodiment of a frame, with the atrialsealing member excluded, comprising wide-set ventricular anchors.

FIG. 44 depicts a series of side views of an exemplary embodiment of aframe, with the atrial sealing member excluded, having ventricularanchors that flip up into a final configuration.

FIG. 45 depicts a series of side views of an exemplary embodiment of aframe, with the atrial sealing member excluded, having ventricularanchors that curl up into a final configuration.

FIGS. 46A-46C show an exemplary embodiment of a frame, with the atrialsealing member excluded, wherein the main body is manufacturedseparately from the ventricular anchors.

FIGS. 47A-47D show another embodiment of a frame, with the atrialsealing member excluded, wherein the main body is manufacturedseparately from the ventricular anchors and attached using a sleeve.

FIGS. 48A-48C show another embodiment of a frame, with the atrialsealing member excluded, wherein the main body is manufacturedseparately from the ventricular anchors and attached using a sleeve witha mechanical lock.

FIG. 49 shows an exemplary embodiment of a delivery system fordelivering and implanting a prosthetic valve at a native mitral valveregion of the heart.

FIG. 50 is a detailed view of the distal portion of the delivery systemof FIG. 49.

FIG. 51 is a cross-sectional view of a handle portion of the deliverysystem of FIG. 49, taken along section line 51-51.

FIG. 52 is a cross sectional view of the handle portion of the deliverysystem of FIG. 49, taken along section line 52-52.

FIG. 53 is a cross sectional view of an insertable portion of thedelivery system of FIG. 49, taken along section line 53-53.

FIG. 54 shows the delivery system of FIG. 49 with a prosthetic valveloaded within a slotted inner sheath with the ventricular anchorsextending outward through slots of the inner sheath.

FIG. 55 is a cross-sectional view of the delivery system of FIG. 49 in adelivery position containing the prosthetic valve within inner and outersheaths and between a nose cone and a tip of a pusher shaft.

FIG. 56 is a cross-sectional view of a distal end portion of thedelivery system of FIG. 49 showing the outer sheath of the deliverysystem retracted such that ventricular anchors extend outward throughslots of the inner sheath.

FIG. 57 is a cross-sectional view of the heart showing the ventricularanchors of the prosthetic valve being pre-deployed in the left ventricleusing the delivery system of FIG. 49.

FIG. 58 is a view of the mitral valve region of the heart from the leftventricle showing the ventricular anchors extending from the slots inthe delivery system and showing the ventricular anchors positionedbetween respective mitral leaflets and the ventricular walls.

FIG. 59 is a cross-sectional view of the heart showing the prostheticvalve being implanted in the mitral valve region using the deliverysystem of FIG. 49 with the native leaflets positioned between theventricular anchors and the inner sheath.

FIG. 60 is a cross-sectional view of the delivery system of FIG. 49showing the slotted inner sheath retracted to a point where theventricular anchors of the prosthetic valve contact a notched retainingband around the slotted inner sheath.

FIG. 61 is a cross-sectional view of the delivery system of FIG. 49showing the slotted inner sheath fully retracted after the band has beenbroken, and the prosthetic valve in an expanded state after being fullydeployed from the sheath.

FIG. 62 is a view of the mitral valve region of the heart from the leftventricle showing an exemplary embodiment of a prosthetic valve fullyimplanted with the mitral leaflets captured between a main body andventricular anchors.

FIG. 63 shows an exemplary embodiment of a prosthetic valve within acatheter sheath for delivering to a native valve region of the heart,according to another embodiment.

FIG. 64 shows the prosthetic valve of FIG. 63 with the catheter sheathpulled back such that the ventricular anchors are free to expand but themain body remains compressed.

FIG. 65 shows the prosthetic valve of FIG. 63 with the outer sheathrecapturing the main body such that only the ventricular anchors areexposed.

FIG. 66 is a cross-sectional view of the heart showing the prostheticvalve of FIG. 65 being implanted in the native mitral valve region usinga transatrial approach.

FIG. 67 is a cross-sectional view of the heart showing the prostheticvalve of FIG. 65 being implanted in the native mitral valve region usinga transeptal approach.

FIG. 68 is a view of the mitral valve region from the left ventricleshowing an embodiment of an atrially delivered prosthetic valve havingventricular anchors extending free of a sheath and positioned betweenthe native mitral valve leaflets and the ventricular walls.

FIG. 69 is a view of the mitral valve region from the left ventricleshowing the prosthetic valve of FIG. 68 fully expanded and anchored tothe native mitral valve leaflets.

FIG. 70 is a cross-sectional view of the heart showing an embodiment ofa docking frame that is secured to the native tissue of mitral valveregion and a separately deployed prosthetic valve that is secured to thedocking frame within the lumen of the docking frame.

FIG. 71 a perspective view of an embodiment of a prosthetic apparatusfor implanting at the native mitral valve region to treat mitralregurgitation.

FIG. 72 is a side view of the prosthetic apparatus of FIG. 71.

FIG. 73 is another side view of the prosthetic apparatus of FIG. 71.

FIG. 74 is an end view of the prosthetic apparatus of FIG. 71.

FIGS. 75-79 are cross-sectional views of the heart showing a transeptaldelivery of the prosthetic apparatus of FIG. 71.

FIG. 80 is a side view of an alternative embodiment of a prostheticapparatus of FIG. 71, comprising prosthetic valve.

FIG. 81 is a partial side view of an alternative embodiment of aprosthetic apparatus of FIG. 71, comprising a Z-cut frame body.

FIG. 82 is a partial side view of an alternative embodiment of aprosthetic apparatus of FIG. 71, comprising a lattice frame body and aprosthetic valve.

FIG. 83 is a partial side view of an alternative embodiment of aprosthetic apparatus of FIG. 71 comprising a helical frame body.

FIGS. 84 and 85 show an exemplary method for implanting an exemplaryprosthetic apparatus having “L” shaped ventricular anchors.

FIGS. 86 and 87 show another exemplary method for implanting anotherprosthetic apparatus having “L” shaped ventricular anchors.

FIG. 88 is ventricular view of the native mitral valve region.

FIG. 89 is a cross sectional view of the human heart showing a stentedprosthetic valve implanted in the mitral annulus via a subvalvularanchoring mechanism, according to one embodiment.

FIGS. 90A and 90B are side views of an embodiment of a stent for aprosthetic mitral valve, having two U-shaped clips, and shown in anexpanded state.

FIGS. 91A-91D are various views of an embodiment of the stent of FIG.89, having two spiraled clips, and shown in an expanded state.

FIGS. 92A and 92B are side views of an embodiment of the stent of FIG.89, having two curved finger-like clips, and shown in an expanded state.

FIG. 93 is a side view of an embodiment of the stent of FIG. 89, havingtwo spiraled finger-like clips, and shown in an expanded state.

FIGS. 94A and 94B are side views of an embodiment of a stent havingcurling anchors.

FIG. 95 are side views of an embodiment of a stent having flip-upanchors.

FIG. 96 shows side views of an embodiment of a stent having bend-upanchors.

DETAILED DESCRIPTION

Described herein are embodiments of prosthetic valves and componentsthereof that are primarily intended to be implanted at the mitral valveregion of a human heart, as well as apparatus and methods for implantingthe same. The prosthetic valves can be used to help restore and/orreplace the functionality of a defective native valve.

The Human Heart

Relevant portions of the human heart are shown in FIGS. 1 and 2. Ahealthy heart has a generally conical shape that tapers to a lower apex38. The heart is four-chambered and comprises the left atrium 4, rightatrium 26, left ventricle 6, and right ventricle 28. The left and rightsides of the heart are separated by a wall generally referred to as theseptum 30. The native mitral valve 2 of the human heart connects theleft atrium 4 to the left ventricle 6. The mitral valve 2 has a verydifferent anatomy than other native heart valves, such as the aorticvalve 14.

The mitral valve 2 includes an annulus portion 8, which is an annularportion of the native valve tissue surrounding the mitral valve orifice,and a pair of cusps, or leaflets, 10, 12 extending downward from theannulus 8 into the left ventricle 6. The mitral valve annulus 8 can forma “D” shaped, oval, or otherwise out-of-round cross-sectional shapehaving major and minor axes. The anterior leaflet 10 can be larger thanthe posterior leaflet 12, as shown schematically in FIG. 4A, forming agenerally “C” shaped boundary between the abutting free edges of theleaflets when they are closed together. FIG. 4B shows the native mitralvalve 2 with a slight gap 3 between the leaflets 10, 12, such as with adefective native mitral valve that fails to completely close, which canlead to mitral regurgitation and/or other undesirable conditions.

When operating properly, the anterior leaflet 10 and the posteriorleaflet 12 function together as a one-way valve to allow blood to flowonly from the left atrium 4 to the left ventricle 6. The left atrium 4receives oxygenated blood from the pulmonary veins 32. When the musclesof the left atrium 4 contract and the left ventricle dilates, theoxygenated blood that is collected in the left atrium 4 flows into theleft ventricle 6. When the muscles of the left atrium 4 relax and themuscles of the left ventricle 6 contract, the increased blood pressurein the left ventricle urges the two leaflets together, thereby closingthe one-way mitral valve so that blood cannot flow back to the leftatrium and is instead expelled out of the left ventricle through theaortic valve 14.

To prevent the two leaflets 10, 12 from prolapsing under pressure andfolding back through the mitral annulus 8 toward the left atrium 4, aplurality of fibrous cords called chordae tendineae 16 tether theleaflets 10, 12 to papillary muscles in the left ventricle 6. Referringto FIGS. 3 and 4, chordae 16 are attached to and extend between thepostero-medial papillary muscle 22 and the postero-medial margins ofboth the anterior leaflet 10 and the posterior leaflet 12 (A1 and P1areas, respectively, as identified by Carpentier nomenclature).Similarly, chordae 16 are attached to and extend between theantero-lateral papillary muscle 24 and the antero-lateral margins ofboth the anterior leaflet 10 and the posterior leaflet 12 (A3 and P3areas, respectively, as identified by Carpentier nomenclature). The A2and P2 areas are relatively free of chordae attachment points andprovide a region where a prosthetic mitral valve can be anchored (seeFIG. 3). In addition, the organization of the chordae provides anapproach path to deliver a prosthetic mitral valve with minimal risk ofchordae entanglement.

Prosthetic Valve

When the native mitral valve fails to function properly, a prostheticvalve replacement can help restore the proper functionality. Compared tothe aortic valve 14, however, which has a relatively round and firmannulus (especially in the case of aortic stenosis), the mitral valveannulus 8 can be relatively less firm and more unstable. Consequently,it may not be possible to secure a prosthetic valve that is designedprimarily for the aortic valve within the native mitral valve annulus 8by relying solely on friction from the radial force of an outer surfaceof a prosthetic valve pressed against the native mitral annulus 8.Accordingly, the prosthetic valves described herein can rely onventricular anchors instead of, or in addition to, radial frictionforces, to secure the prosthetic valve within the native mitral valveannulus 8 (see FIG. 23, for example).

In addition to providing an anchoring means for the prosthetic valve,the ventricular anchors can also remodel the left ventricle 6 to helptreat an underlying cause of mitral regurgitation—left ventricleenlargement/dilation. The ventricular anchors can pull the native mitralvalve leaflets 10, 12 closer together and toward the left atrium and,via the chordae 16, thereby pull the papillary muscles 22, 24 closertogether, which can positively remodel the ventricle acutely and preventthe left ventricle from further enlarging. Thus, the ventricular anchorscan also be referred to as tensioning members or reshaping members.

FIGS. 5-7 illustrate an exemplary prosthetic valve 100, according to oneembodiment, that can be implanted in the native mitral valve region ofthe heart to replace the functionality of the native mitral valve 2. Theprosthetic valve 100 comprises a frame 102 and a valve structure 104supported by and/or within the frame. The valve structure 104 caninclude a plurality of prosthetic leaflets 106 (three in the illustratedembodiment) and/or other components for regulating the flow of blood inone direction through the prosthetic valve 100. In FIGS. 5 and 6, forexample, valve structure 104 is oriented within the frame 102 such thatan upper end 110 of the valve structure is the inflow end and a lowerend 112 of the valve structure is the outflow end. The valve structure104 can comprise any of various suitable materials, such as naturaltissue (e.g., bovine pericardial tissue) or synthetic materials. Thevalve structure 104 can be mounted to the frame 102 using suitabletechniques and mechanisms. In the illustrated embodiment, for example,the leaflets 106 are sutured to the frame 102 in a tricuspidarrangement, as shown in FIG. 7.

Additional details regarding components and assembly of prostheticvalves (including techniques for mounting leaflets to the frame) aredescribed, for example, in U.S. Patent Application Publication No.2009/0276040 A1 and U.S. patent application Ser. No. 12/393,010, whichare incorporated by reference herein.

As shown in FIGS. 8-10, the frame 102 can comprise a tubular main body122, one or more ventricular anchors 126 extending from a ventricularend 130 of the main body and optionally an atrial sealing member 124extending radially outward from an atrial end 132 of the main body. Whenthe frame 102 is implanted in the native mitral valve region of theheart, as shown in FIG. 23, the main body 122 is positioned within thenative mitral valve annulus 8 with the ventricular end 130 of the mainbody 122 being a lower outlet end, the atrial end 132 of the main body132 being an upper inlet end, the ventricular anchors 126 being locatedin the left ventricle 6, and the atrial sealing member 124 being locatedin the left atrium 4.

The frame 102 can be made of a wire mesh and can be radially collapsibleand expandable between a radially expanded state and a radiallycompressed state (as shown schematically in a series of successivestages in FIGS. 11-16 and 17-22) to enable delivery and implantation atthe mitral valve region of the heart (or within another native heartvalve). The embodiments of the frame 102 shown in FIGS. 11-22 do notinclude an atrial sealing member 124, though other embodiments of theframe 102 do include an atrial sealing member 124. The wire mesh caninclude metal wires or struts arranged in a lattice pattern, such as thesawtooth or zig-zag pattern shown in FIGS. 8-10 for example, but otherpatterns may also be used. The frame 102 can comprise a shape-memorymaterial, such as Nitinol for example, to enable self-expansion from theradially compressed state to the expanded state. In alternativeembodiments, the frame 102 can be plastically expandable from a radiallycompressed state to an expanded state by an expansion device, such as aninflatable balloon (not shown) for example. Such plastically expandingframes can comprise stainless steel, chromium alloys, and/or othersuitable materials.

In an expanded state, as shown in FIGS. 8-10, the main body 122 of theframe 102 can form an open-ended tube. The valve structure 104 can becoupled to an inner surface of the frame 102, such as via a materiallayer 142 on the inner surface of the frame, as discussed below, and canbe retained within the lumen formed by the main body 122, as shown inFIG. 7. An outer surface of the main body 122 can have dimensionssimilar to that of the mitral orifice, i.e., the inner surface of themitral annulus 8, but not necessarily. In some embodiments, for example,the outer surface of the main body 122 can have diametrical dimensionsthat are smaller than the diametrical dimensions of the native mitralorifice, such that the main body 122 can fit within the mitral orificein the expanded state without substantially stretching the native mitralannulus 8, such as in FIG. 23. In such embodiments, the frame 102 neednot rely on a pressure fit, or friction fit, between the outer surfaceof the main body 122 and the inner surface of the mitral annulus 8 forprosthetic valve retention. Instead, the frame 102 can rely on theventricular anchors 126 and/or the atrial sealing member 124 forretention, as further described below. In other embodiments, however,the main body 122 can be configured to expand to an equal or greatersize than the native mitral orifice and thereby create a pressure fitwhen implanted.

In embodiments wherein the main body 122 comprises diametricaldimensions that are smaller than the diametrical dimensions of thenative mitral orifice, the main body can sit loosely, or “float,”between the native leaflets 10, 12. As shown in FIG. 4C, this loose fitcan create gaps 37 between the leaflets 10, 12 and the main body 122 ofthe frame. To prevent blood flow between the outside of the prostheticvalve 100 and the native valve tissue, such as through the gaps 37, theannular atrial sealing member 124 can create a fully annular contactarea, or seal, with the native tissue on the atrial side of the mitralannulus 8. Accordingly, as shown in FIG. 4D, the atrial sealing member124 can be sized to fully cover the gaps 37.

The ends of the frame 102 can have a sawtoothed or zig-zag pattern, asshown in FIGS. 8-10, comprising a series of side-by-side “V” shapedportions connected together at their upper ends, for example. Thispattern can facilitate compression and can help maximize a surface areawith which the frame connects to the native tissue. Alternatively, theends of the frame 102 can have a straight edge, or some other pattern.

In some embodiments, the main body 122 can comprise at least oneextension member, or pushing member, that extends downward from theventricular end 130 of the main body 122. The frame 202 shown in FIG.25, for example, comprises an extension member in the form of a prong204 that extends from the lower vertex of one of the “V” shaped portionsof a main body 222. The prong 204 can have an upside-down “T” shapecomprising a lower pushing surface 206. In another embodiment, the frame302 shown in FIG. 26 comprises a “V” shaped pushing member 304 thatextends from two adjacent lower vertices of a main body 322 andcomprises a pushing surface 306. The pushing surfaces 206 and 306 cancomprise the lowermost points on the frames 202 and 302, respectively,and can provide a pushing surface for the frame to be expelled out of adelivery device without contacting the ventricular anchors 226, 326, asdescribed in more detail below.

With reference again to the embodiment shown in FIGS. 8-10, the atrialsealing member 124 of the frame 102 can be integral with the main body122 and can be comprised of the same wire mesh lattice as the main body122 such that the atrial sealing member 124 can also be radiallycollapsible and expandable. In the expanded state, the atrial sealingmember 124 can be generally frustoconical and extend from the atrial end132 of main body 122 both radially outward and axially downward towardthe ventricular end 130 of the main body 122. An outer rim 140 of theatrial sealing member 124 can be sized and shaped to contact the atrialside of the mitral annulus and tissue of the left atrium 8 when theframe 102 is implanted, as shown in FIG. 23. The end view profile of theouter rim 140, as shown in FIG. 10, can have a generally circular, oval,or other shape that generally corresponds to the native geometry of theatrial walls 18 and the mitral annulus 8. The contact between the atrialsealing member 124 and the tissue of the atrial walls 18 and/or themitral annulus 8 can promote tissue ingrowth with the frame, which canimprove retention and reduce paravalvular leakage.

The atrial sealing member 124 desirably is sized such that when theprosthetic valve 100 is implanted in the native mitral valve, as shownin FIG. 23, the outer rim 140 contacts the native annulus 8 around theentire native valve and therefore completely covers the opening betweenthe native leaflets 10, 12. The atrial sealing member 124 desirablyincludes a sealing layer 142 that is impervious to the flow of blood. Inthis manner, the atrial sealing member 124 is able to block blood fromflowing back into the left atrium between the outer surfaces of theprosthetic valve 100 and the native valve tissue. The atrial sealingmember also ensures that all, or substantially all, of the blood passesthrough the one-way valve as it flows from the left atrium to the leftventricle.

As shown in FIGS. 5-7, at least one biocompatible sheet or layer 142 canbe connected to the inner and/or outer surfaces of the main body 122 andthe atrial sealing member 124 to form at least one layer or envelopecovering the openings in the wire mesh. The layer 142 can be connectedto the frame 102 by sutures, for example. The layer 142 can form afluid-occluding and/or sealing member that can at least partially blockthe flow of blood through the wire mesh to reduce paravalvular leakageand can promote tissue ingrowth with the frame 102. The layer 142 canprovide a mounting surface, or scaffold, to which the portions of thevalve structure 104, such as the leaflets 106, can be secured. Forexample, the dashed line 108 in FIGS. 5 and 6 represents where the inletends of the leaflets 106 can be sewn, sutured, or otherwise secured tothe layer 142. This seam between the inlet ends of the leaflets 106 andthe layer 142 can form a seal that is continuous around the innerperimeter of the layer 142 and can block blood flow between the innersurface of the layer 142 and the outer surface of the leaflets 106. Thisseal can allow the prosthetic valve 100 to direct blood to flow betweenthe plurality of leaflets 106.

The same layer 142 and/or one or more separate cuffs 144 can also wraparound, or cover, the end edges of the frame 102, such as theventricular end 130 of the main body 122 and/or the outer rim 140 of theatrial sealing member 124. Such a cuff 144 can cover and protect sharpedges at the ends of the frame 102. For example, in the embodiment shownin FIG. 5, the layer 142 extends from the outer rim 140 across the uppersurface of the atrial sealing member 124 and downward along the innersurface of the main body 122 and comprises a cuff 144 that wraps aroundand covers a ventricular end portion of the main body 122. The layer 142can be sutured to the outer rim 140 and to the inner surface of the mainbody 122.

The layer 142 can comprise a semi-porous fabric that blocks blood flowbut can allow for tissue ingrowth. The layer 142 can comprise syntheticmaterials, such as polyester material or a biocompatible polymer. Oneexample of a polyester material is polyethylene terephthalate (PET).Alternative materials can be used. For example, the layer can comprisebiological matter, such as natural tissue, pericardial tissue (e.g.,bovine, porcine, or equine pericardium) or other biological tissue.

With reference to FIGS. 8 and 9, one or more ventricular anchors 126 canextend from the main body 122 of the frame 102, such as from theventricular end 130 of the main body. The ventricular anchors 126 canfunction to retain the frame 102, with or without the valve structure104, within a native valve region of the heart. In the embodiment shownin FIGS. 8 and 9, the frame 102 comprises two diametrically opposedventricular anchors 126 that can function to secure the frame 102 to theanterior and posterior mitral leaflets 10, 12, respectively, when theframe 102 is implanted in the mitral valve region, as shown in FIG. 23.In alternate embodiments, the frame 102 can have three or moreventricular anchors 126, which can be angularly spaced around the mainbody 122 of the frame.

When the frame 102 is in an expanded state, as in FIG. 9, the geometryof the frame can cause the ventricular anchors 126 to be urged againstthe outer surface of the main body 122. Alternatively, the ventricularanchors 126 can be configured to be spaced apart from the outer surfaceof the main body 122 when the frame 102 is in the expanded state (seeFIG. 39, for example). In any case, when the frame 102 is radiallycompressed to the compressed state, the space or gap between theventricular anchors 126 and the outer surface of the main body 122 canincrease, as shown in FIGS. 11-16.

While the main body 122 and the atrial sealing member 124 are in thecompressed state, the frame 102 can be inserted into the mitral valveorifice such that the spaced apart ventricular anchors 126 wrap aroundthe leaflets 10, 12 and extend upward between the leaflets and theventricular walls 20 (see FIG. 59, for example). With reference to FIG.23, an anterior ventricular anchor 146 can be located behind theanterior leaflet 10 and a posterior ventricular anchor 148 can belocated behind the posterior leaflet 12. With reference to FIGS. 3 and4, the two ventricular anchors are desirably located behind therespective leaflets near the middle portions of the leaflets A2, P2about midway between the commissures 36 where the two leaflets meet.These middle portions A2, P2 of the leaflets 10,12 are desirableventricular anchor locations because the chordae tendineae 16attachments to the leaflets are sparser in these locations compared tolocations nearer to the commissures 36.

When the main body 122 is subsequently expanded or allowed toself-expand to the expanded state, as shown in FIGS. 11-16 in reverseorder, the ventricular anchors are configured to pivot radially inwardrelative to the main body 122, without external compressive forces onthe ventricular anchors. This causes the gaps between the ventricularanchors 126 and the outer surface of the main body 122 to decrease,thereby enabling the capture of the leaflets 10, 12 between theventricular anchors and the main body. Conversely, compressing the mainbody 122 causes the ventricular anchors 126 to pivot away from the mainbody to increase the gaps between the outer surface of the main body andthe ventricular anchors. In some embodiments, the free ends, or apexes,162 of the ventricular anchors 126 can remain substantially the samedistance apart from one another as the main body 122 is radiallycompressed or expanded free of external forces on the ventricularanchors. In some embodiments, such as the embodiment shown in FIG. 23,the frame is configured to compress the native mitral leaflets 10, 12between the main body and the ventricular anchors when the frame expandsto the expanded state. In other embodiments, such as the embodimentshown in FIG. 39, the ventricular anchors do not compress or clamp thenative leaflets against the main body but still prevent the prostheticvalve from migrating toward the left atrium by the hooking of theventricular anchors around the native leaflets 10, 12. In suchembodiments, the prosthetic valve 100 can be retained in place againstmigration toward the left ventricle by the atrial sealing member 124 asfurther described below.

With reference to the embodiment shown in FIGS. 8-10, each ventricularanchor 126 can comprise a flexible, elongate member, or wire, 150comprised of a shape memory material, such as, for example, Nitinol. Insome embodiments, as shown in FIG. 8, each wire 150 can comprise a firstend portion 152 coupled to a first attachment location 156 of the mainbody 122, and a second end portion 154 coupled to a second attachmentlocation 158 of the main body. The first and second end portions 152,154 form a base of the ventricular anchor. The first and secondattachment locations 152, 154 of the main body can be at, or adjacentto, the ventricular end 130 of the main body 122. The two end portions152, 154 of each wire 150 can be extensions of the wires or struts thatmake up the lattice mesh of the main body 122. Each wire 150 furthercomprises an intermediate portion 160 extending in a directionlengthwise of the main body between the end portions 152, 154. Theintermediate portion 160 includes a bend 162 that forms the free endportion, or apex, of the ventricular anchor.

The wire 150 can have a circular or non-circular cross-sectional profileperpendicular to a length of the wire, such as a polygonalcross-sectional profile. With reference to FIG. 8A, the wire 150 cancomprise a rectangular cross-sectional shape having a length “L” and arelatively narrower width “W” such that when the two end portions 152,154 of the ventricular anchor 126 attached to the frame 102 are movedtoward each other, such as when the frame is compressed, the wire 150bends primarily in the width direction. This promotes bending of theventricular anchor 126 in a direction radially outward away from themain body 122, widening the gap between the ventricular anchor 126 andthe main body 122. This feature can help to capture a leaflet betweenthe ventricular anchor 126 and the main body 122 during implantation.

Ventricular anchors can comprise various shapes or configurations. Someframe embodiments, such as the frame 102 shown in FIG. 8, comprisegenerally “U” or “V” shaped ventricular anchors 126 that connect to themain body 122 at two attachment locations 156, 158. The upper apex 162of the ventricular anchors 126 can function like a wedge to facilitatemoving the ventricular anchors behind respective leaflets whileminimizing the risk of chordae entanglement. The end portions 152, 154of each wire 150 can extend downward from attachment locations 156, 158,respectively, at the ventricular end 130 of the main body 122. The wire150 can then curve back upward from each end portion 152, 154 toward theapex 162.

The wires 150 can be covered by biocompatible materials, such as in theembodiment shown in FIGS. 5-7. A first material 164 can be wrappedaround, or coat, at least some portion of the wire 150. A secondmaterial 166 can span across two portions of the wire 150 to form a web,which can improve tissue ingrowth. The first and second materials 164,166 can comprise the same material or different materials, such as abiocompatible semi-porous fabric, for example. The covering materials164, 166 can increase tissue ingrowth with the ventricular anchor 126 toimprove retention. Furthermore, the covering materials can decrease thefrictional properties of the ventricular anchors 126 to facilitateimplantation and/or increase the frictional properties of theventricular anchors to improve retention.

FIG. 24 shows exemplary dimensions of the embodiment of the frame 102shown in FIG. 9. The diameter “Dmax” of the outer rim 140 of the atrialsealing member 124 can range from about 50 mm to about 70 mm, and isabout 50 mm in one example. The diameter “Dbody” of the outer surface ofthe main body 122 can range from about 23 mm to about 50 mm, and isabout 29 mm in one example. The distance “W1” between the two attachmentpoints 156, 158 for one ventricular anchor 126 can range from about 8 mmto about 50 mm, and is about 25 mm in one example. The overall axialheight “Hmax” of the frame 102 can range from about 20 mm to about 40mm, and is about 30 mm in one example. The axial height “H1” from theouter rim 140 to the lowermost portion 168 of the ventricular anchors126 can range from about 10 mm to about 40 mm, and is about 23 mm in oneexample. The axial distance “H2” from the apex 162 of the ventricularanchor 126 to the lowermost portion 168 of the ventricular anchor 126can range from about 10 mm to about 40 mm, and is about 18 mm in oneexample. The axial distance “H3” from the lower end 130 of the main body122 to the lowermost portion 168 of the ventricular anchor 126 can rangefrom about 0 mm to about 10 mm, and is about 5 mm in one example.

Some frame embodiments comprise more than two ventricular anchors. Forexample, a frame can have two or more ventricular anchors configured toattach to multiple locations along a single leaflet of a native valve.In some such embodiments (not shown), the frame can comprise twoventricular anchors that attach to the anterior mitral leaflet 10 and/ortwo ventricular anchors that attach to the posterior mitral leaflet 12.Ventricular anchors can also attach to other regions of the leafletsinstead of, or in addition to, the A2 and P2 regions.

Some prosthetic valve embodiments comprise four ventricular anchorsspaced evenly apart around a main body. FIGS. 27-32 show one suchprosthetic valve embodiment 400 comprising a frame 402 that comprises apair of ventricular anchors 426 on diametrically opposed sides of a mainbody 422 and a pair of diametrically opposed commissure anchors 428located about midway between the ventricular anchors 426. Theventricular anchors 426 extend downward from attachment points 456 and458 and comprise a neck portion 450 (see FIG. 31). These ventricularanchors 426 can function similarly to the ventricular anchors 126 of theframe 102 to capture leaflets and retain the frame 402 within the mitralorifice, as shown in FIG. 33. The commissure anchors 428 can extendupward from the same attachment locations 456, 458 on the main body 422(see FIG. 30). While the ventricular anchors 426 can clip the mitralleaflets 10, 12 at the A2 and P2 regions, respectively, the commissureanchors 428 can hook around and extend upward behind the mitralcommissures 36, not compressing the leaflets. The apexes 464 of thecommissure anchors 428 can extend upward to abut the ventricular side ofthe mitral annulus 8 and compress the mitral annulus 8 between the outerrim 440 of the atrial sealing member 424 and the apexes 464 of thecommissure anchors 428. This compression of the mitral annulus 8 canprovide additional retention against both atrial and ventricularmovement.

Other frame embodiments can comprise more than four ventricular anchors.For example, a frame can comprise six or more ventricular anchors thatcan engage multiple locations on the leaflets 10, 12 and/or thecommissures 36.

FIG. 34 shows a frame embodiment 502 that comprises extended ventricularanchors 526 that are configured to extend around the ends of theleaflets 10, 12 and extend upward behind the leaflets to locationsproximate the outer rim 540 of a downwardly extending frustoconicalatrial sealing member 524. The upper apexes 562 of the extendedventricular anchors 526 contact the ventricular surface of the mitralannulus 8 and/or portions of the native leaflets 10, 12 adjacent to theannulus, or annulus connection portions of the leaflets, while the outerrim 540 of the atrial sealing member 524 contacts the atrial surface ofthe mitral annulus and/or the annulus connection portions of theleaflets. The extended ventricular anchors 526 and the atrial sealingmember 524 can be configured to oppose one another and desirablycompress the mitral annulus 8 and/or annulus connection portions of theleaflets 10, 12 to retain the frame 502 from movement in both the atrialand ventricular directions. Thus, in this embodiment, the ventricularanchors 526 need not compress the native leaflets 10, 12 against theouter surface of the main body 522 of the frame. Instead, as shown inFIG. 34, the leaflets 10, 12 can be captured loosely between theextended ventricular anchors 526 and the outer surface of the main body522.

FIGS. 35 and 36 show a frame embodiment 602 comprising necked, “S”shaped ventricular anchors 626. From the side view of FIG. 35, the “S”shape of the ventricular anchors 626 is apparent. Starting from oneattachment point A on the ventricular end 630 of the main body 622, theventricular anchor wire 650 extends downward and radially outward fromthe main body to a point B, then curves upward and outward to a point C,then curves upward and inward to a point D, and then curves upward andback outward to an uppermost point, or apex, E. The ventricular anchorwire 650 then continues to extend back to the second attachment pointfollowing a similar, but mirrored path. From the frontal view of FIG.36, the ventricular anchor wire 650 forms a necked shape that issymmetrical about a longitudinal center axis 690 extending through thecenter of the main body 622, forming two mirrored halves. Each half ofventricular anchor wire 650 begins at an attachment point A on theventricular end 630 of the main body 622, curves downward and inward(toward the other half) to point B, then curves upward and inward to anecked portion at point C, then curves upward and outward (away from theother half) to a point D, then curves upward and inward again to anuppermost point, or apex, E where the two halves join together.Referring to FIG. 35, the radial distances from a longitudinal centeraxis 690 of the main body 622 to points C and E are both greater thanthe radial distances from the axis 690 to points D. Furthermore, thedistance between the two points C is less than the distance between thetwo points D. The “S” shaped ventricular anchor 626 can help distributestresses more evenly along the wire 650 and reduce stress concentrationsat certain locations, such as the attachment points A.

FIGS. 37 and 38 show a frame embodiment 702 that comprises two widershaped ventricular anchors 726. Each wider shaped ventricular anchors726 comprises a necked mid portion 780 and a broad upper portion 782.The upper portion 782 can extend generally parallel to the inflowopening of the frame 702 and can be curved around the outer surface of amain body 722. This wider shape can increase surface contact with thenative leaflet and/or other cardiac tissue to reduce pressure andthereby reduce abrasion. In some embodiments, the broad upper portion782 of the wider shaped ventricular anchors 726 can have a curvaturethat corresponds to the curvature of the outer surface of the main body722 (see FIG. 38) to further improve tissue contact. The wider shapedventricular anchor can have a longer surface contact with the atrialsealing member; thereby increasing retention performance and reducingparavalvular leak.

FIG. 39 shows a frame embodiment 802 comprising ventricular anchors 826that are configured to define a separation, or gap, between the anchorsand the main body 822 even after the frame 802 expands (although theanchors 826 can otherwise function similar to ventricular anchors 126,such that the gaps between the anchors 826 and the frame main body 822can increase and decrease upon compression and expansion of the mainbody, respectively, to facilitate placement of the anchors 826 behindthe native leaflets). The gap can be sized to facilitate capturing thenative leaflets 10, 12 with little or no compression of the nativeleaflets. Since little or no leaflet compression occurs, this frameembodiment 802 can minimize trauma to the native leaflets. Instead ofcompressing the leaflets 10, 12 for valve retention, the ventricularanchors 826 can hook the ventricular edges 40, 42 of the leaflets 10,12, respectively, while an atrial sealing member 824 of the framepresses downwardly on the atrial side of the mitral valve annulus 8. Thecontact between the atrial sealing member 824 and the annulus 8 causesthe main body 822 to shift slightly upwardly pulling the ventricularanchors 826 upwardly against the ventricular edges of the leaflets 10,12. The upward force of the ventricular anchors in conjunction withdownward tension on the leaflets from the chordae tendineae 16 restrainthe implant from moving upward toward the left atrium 4.

FIG. 40 shows a frame embodiment 902 that comprises a main body 922,ventricular anchors 926 and a disk-like atrial sealing member 924 thatextends radially outward from the upper end 932 of the main body 922. Inthis embodiment, the atrial sealing member 924 extends substantiallyperpendicular to the frame opening defined by the upper and 932 ratherthan downwardly toward the frame's lower end 930. The disk-like atrialsealing member 924 can be positioned flat across the top surface of themitral annulus 8 and provide increased surface area contact for tissueingrowth.

FIGS. 41 and 42 show frame embodiments 1002 and 1012, respectively, thatcomprise an atrial sealing member 1024 having a generally frustoconicalportion 1028 that extends from the upper end 1032 of a main body 1022both radially outward and axially upward away from the main body. Theatrial sealing member 1024 can also include a generally cylindricalupper, or inlet, portion 1029 that extends further upward from thefrustoconical portion 1028 opposite the upper end 1032 of the main body1022. The atrial sealing member 1024 can generally correspond to theshape of the atrial walls 18 adjacent to the mitral annulus 8 andprovide for increased contact area between the atrial wall tissue andthe atrial sealing member 1024. The frame 1002 includes ventricularanchors 1026 that extend from a ventricular end 1030 of the main body1022 and along the majority of the length of the main body.

The frame 1012 shown in FIG. 42 comprises extended ventricular anchors1050. The extended anchors 1050 can extend from the ventricular end 1030of the main body 1022 along the outer surface of the main body and bendradially outward to form upper portions 1060 that extend along the lowersurface of the frustoconical portion 1028. This configuration can allowthe extended ventricular anchors 1050 to trap more of the leaflets 10,12 and/or the mitral annulus 8 against the frame, thereby reducingparavalvular leakage and improving tissue ingrowth and retention.

FIG. 43 shows a frame embodiment 1102 having ventricular anchors 1126that have shorter moment arms D2 compared to the ventricular anchors 126of the frame 102 shown in FIG. 9. The shorter moment arms D2 can resultin reduced torque at the ventricular anchor attachment points 1156,1158. The distance D2 can be reduced by increasing the distance D1between the attachment points 1158 and 1156 on the main body 1122 ofneighboring ventricular anchors 1126. The distance D1 between theventricular anchors 1126 of the frame 1102 is greater than the distanceD1 between the attachment points 158 and 156 of frame 102 (see FIG. 9),thus shortening the moment arm D2 of the force F relative to theattachment point 1156. The reduced torque at the attachment points 1156and 1158 can reduce fatigue and thus improve the durability of the frame1102.

Some embodiments of ventricular anchors can optionally also comprise oneor more barbs (not shown) that can protrude radially from a ventricularanchor toward the ventricular walls 20 or toward the leaflets 10, 12.Such barbs can help retain a frame, particularly against movementtowards the left ventricle 6.

FIGS. 44A-44D illustrate a frame embodiment 1202 comprising “flip-up”ventricular anchors 1226. Each ventricular anchor 1226 can befinger-like and can extend from only one attachment point on the lowerend 1230 of the main body 1222. Alternatively, each ventricular anchorcan comprise a wire or similar element that extends from two attachmentpoints on the main body 1222. In the illustrated embodiment, theventricular anchors 1226 can be pre-formed to extend along the outerside of the main body 1222 in the functional, deployed state, as shownin FIG. 44D. During delivery, the ventricular anchors 1226 can bepartially or completely straightened, as shown in FIG. 44A, and retainedin that state by a delivery device, such as a sheath. As the frame 1202is advanced from the sheath, for example, the ventricular anchors 1226spring back to their pre-formed shape, as shown in FIGS. 44B-44D,capturing the leaflets 10, 12 between the ventricular anchors 1226 andthe main body 1222.

FIGS. 45A-45E represent a frame embodiment 1302 comprising “bend-up” or“curl-up” ventricular anchors 1326. As with the ventricular anchors 1226of FIG. 44, each ventricular anchor 1326 can be finger-like and/or canextend from two or more points on lower end 1330 of the main body 1322.The ventricular anchors 1326 can be pre-formed in a curved shape, asshown in FIG. 45E, that extends along the side of the main body 1322 inthe deployed state. During delivery, the ventricular anchors 1326 can bepartially or completely straightened, as shown FIG. 45A, and retained inthat state by a delivery device, such as a sheath. As the frame 1302 isadvanced from the sheath, for example, the ventricular anchors 1326 areallowed to spring back to their pre-formed curved shape, as shown inFIGS. 45B-45E, capturing the leaflets 10, 12 between the ventricularanchors 1326 and the main body 1322.

In some frame embodiments, one or more ventricular anchor components canbe formed separately from the main body and later assembled together toform a frame. In one such frame embodiment 1402, as shown in FIGS.46A-46C, a main body 1422 is formed separately from at least oneventricular anchor portion 1424. The ventricular anchor portions 1424can comprise one or more ventricular anchors 1426 extending from an atleast partially annular base 1432, which can comprise side-by-side “V”shaped strut portions connected together at their upper ends. The lowerends of the ventricular anchors 1426 in the illustrated embodiment areconnected to the base 1432 at the lower vertexes of the “V” shapedportions. After the main body and the ventricular anchor portions areseparately formed, the ventricular anchor portions 1424 can be attachedto the lower portion 1430 of the main body 1422. For example, the bases1432 can be placed on opposite sides of the outer surface of the mainbody 1422 and then sewn, welded, or otherwise attached to the lowerportion 1430 of the main body 1422 in a suitable manner, such as byusing a locking mechanism. The bases 1432 can be attached to the mainbody 1422 such that the “V” shaped portions of the bases overlap withcorresponding “V” shaped portions of the lower end 1430 of the main body1422. In some embodiments, the ventricular anchor portion 1424 cancomprise a complete ring having all of the ventricular anchors 1426extending from one annular base such that the ventricular anchors arepre-spaced relative to one another. The annular base can then beattached around the lower end 1430 of the main body 1422. In otherembodiments, multiple ventricular anchor portions 1424, each having oneor more ventricular anchors 1426 extending from a respective base 1432comprising a partial ring, are secured to the main body 1422.

FIGS. 47A-47D and FIGS. 48A-48C show alternative frame embodimentswherein one or more ventricular anchor components are formed separatelyfrom a main body and later assembled together to form a frame. In theseframe embodiments, the main body can comprise attachment portions towhich anchor portions can be attached using sleeves. For example, FIGS.47A-47D show an exemplary frame 1500 comprising a main body 1502 havingat least two ventricular anchor attachment portions 1508 and at leastone ventricular anchor 1504 having two attachment portions 1510connected to respective attachment portions 1508 with respective sleeves1506. Similarly, FIG. 48A-48C show an exemplary frame 1600 comprising amain body 1602 having at least two ventricular anchor attachmentportions 1608 and at least one ventricular anchor 1604 having twoattachment portions 1610 connected to respective attachment portions1608 with respective sleeves 1606. The sleeves can comprise, forexample, a metal material, such as Nitinol, having superelastic and/orshape-memory characteristics. In some embodiments, the sleeves cancomprise metal of an anneal state suitable for a crimping process. Thesleeves can be attached to the anchor portions and to the attachmentportions of the main body by any suitable attachment means, such as bywelding. As shown in FIGS. 48A-48C, the attachment portion 1610 of theanchors 1604 and the attachment portions 1608 of the main body 1602 cancomprise geometric features, such as narrow regions, or cut-outs, whichallow the sleeves 1606 to integrate the anchor portions 1604 to the mainbody 1602, such as by forming a mechanical lock.

Multi-part construction of a frame, as shown in FIG. 46-48, can reducestrain and fatigue at the ventricular anchor attachment locationscompared to a unibody, or one-piece, construction. By contrast, in someembodiments comprising a unibody construction, the ventricular anchorsare initially laser cut and expanded such that they extend downward fromthe lower end of the main body, and are then formed, or bent, to adesired configuration adjacent to the outside of the main body of theframe. Such bending can strain and weaken the bent portion.

To avoid strain caused by plastic deformation of the ventricularanchors, the ventricular anchors can be pre-formed in a desiredimplantation (deployed) shape without plastically bending theventricular anchors. The ventricular anchors can then be elasticallydeformed, such as straightened and/or compressed, to fit into a deliverydevice for delivery through the body to the mitral valve region of theheart. The deformed ventricular anchors can resiliently regain theirpre-formed shape once freed from the axial constraint of a deliverydevice to facilitate capturing the leaflets 10, 12 between theventricular anchors and the main body of the frame.

Any of the various embodiments of frames described above can be combinedwith a fluid-occluding member, such as valve structure 104, to form afully assembled prosthetic valve that can be implanted within the nativemitral valve. In other embodiments, any of the frames described abovecan be provided without a fluid-occluding member and can be used as ascaffolding or docking structure for receiving a separate prostheticvalve in a two-stage delivery process. With reference to the exemplaryembodiment shown in FIG. 70, a docking frame 103 (which can have aconstruction similar to the frame 102) can be deployed first, forexample by any of the anchoring techniques discussed above. Then, aseparate prosthetic valve 114 can be delivered and deployed within thelumen formed by the previously deployed docking frame 103. The separateprosthetic valve 114 desirably comprises a radially compressible andexpandable frame 116 that mounts a fluid-occluding member (not shown inFIG. 70), such as the valve structure 104 (see FIG. 7) having aplurality of leaflets 106. When expanded inside the docking frame 103,the frame 116 of the prosthetic valve 114 engages the inside surface ofthe docking frame 103 so as to retain, such by friction or mechanicallocking feature, the prosthetic valve 114 within the docking frame 103.Examples of prosthetic valves that can be used in such a two-stageprocess are disclosed in U.S. Pat. No. 7,510,575, which is incorporateherein by reference. In particular embodiments, the prosthetic valve cancomprise any of various transcatheter heart valves, such as the Sapienvalve, available from Edwards Lifesciences LLC (Irvine, Calif.).

The technique of capturing the leaflets 10, 12 between a ventricularanchor and the main body of a frame, such as shown in FIG. 23, canprovide several advantages. First, this can allow for anchoring onto thenative leaflets 10, 12 for retention within the mitral valve region.Second, this technique can utilize the native chordae 16 for retention.Third, this technique can prevent the anterior leaflet 10 from being“pulled” toward the aortic valve 14 when the left ventricle 6 contractsand blood rushes out through the aortic valve (systolic anteriormotion). Fourth, this technique tends to force the native leaflets 10,12 to collapse around the main body of the frame, which can reduceleakage between the outside of the prosthetic valve 100 and the nativemitral valve 2. Fifth, this technique allows for implantation fromeither the left atrium 4 or from the left ventricle 6, as described indetail below.

As described above, various frame embodiments can utilize one or moreanchoring techniques other than compressing the leaflets 10, 12 toretain the prosthetic valve 100 in a desired position within the mitralvalve orifice. These anchoring techniques can include, for example,utilizing tension of the native chordae 16, extending the ventricularanchor length such that the apex of the ventricular anchor is pressed upagainst the mitral annulus 8 so as to form a stop, and compressing themitral annulus 8 and/or atrial tissue between the apex of an ventricularanchor and the outer rim of an atrial sealing member of the frame.

Delivery Approaches

The various methods and apparatus described hereinafter for delivery andimplantation at the native mitral valve region are described withrespect to the prosthetic valve 100, though it should be understood thatsimilar methods and apparatus can be used to deliver and/or implant acomponent of the prosthetic valve 100, such as the frame 102 without thevalve structure 104, or other prosthetic apparatus.

The prosthetic valve 100 can be delivered to the mitral valve regionfrom the left ventricle 6 or from the left atrium 4. Because of theanatomy of the native mitral valve 2, different techniques and/orequipment can be used depending on the direction the prosthetic valve100 is delivered.

Delivery from the ventricular side of the mitral annulus 8 can beaccomplished in various manners. For example, the prosthetic valve 100can be delivered via a transapical approach in which access is made tothe left ventricle 6 via the heart apex 38, as shown in FIG. 57.

Delivery from the atrial side of the mitral annulus 8 can also beaccomplished in various manners. For example, a transatrial approach canbe made through an atrial wall 18, as shown in FIG. 66, for example byan incision through the chest. An atrial delivery can also be made froma pulmonary vein 32 (see FIG. 1). In addition, atrial delivery can bemade via a transeptal approach, as shown in FIG. 67, wherein an incisionis made in the atrial portion of the septum 30 to allow access from theright atrium 26, such as via the inferior or superior vena cava 34.

Ventricular Approaches

One technique for delivering a compressed prosthetic apparatus, such asthe prosthetic valve 100, to the mitral valve region includes accessingthe native mitral valve region from the left ventricle 6, one examplebeing the transapical approach. Alternatively, access to the leftventricle 6 can be made through the aortic valve 14. In the transapicalapproach, access to the left ventricle 6 can be made through an incisionin the chest and an incision at the heart apex 38, as shown in FIG. 57.A transapical delivery system can be used with the transapical approach.

FIGS. 49-53 show an exemplary transapical delivery system, or deliverytool, 2000 that is configured to deliver and implant the prostheticvalve 100. The delivery system 2000 can comprise a series of concentricshafts and sheaths aligned about a central axis and slidable relative toone another in the axial directions. The delivery system 2000 cancomprise a proximal handle portion 2002 for physician manipulationoutside of the body while a distal end portion, or insertion portion,2004 is inserted into the body.

The delivery system 2000 can comprise an inner shaft 2006 that runs thelength of the delivery system and comprises a lumen 2008 through which aguidewire (not shown) can pass. The inner shaft 2006 can be positionedwithin a lumen of a pusher shaft 2010 and can have a length that extendsproximally beyond the proximal end of the pusher shaft and distallybeyond the distal end of the pusher shaft. The delivery system 2000 cancomprise an annular space 2012 between the outer surface of the innershaft 2006 and the inner surface of the pusher shaft 2010. This annularspace can be used for flushing with saline or for allowing blood to beexpelled distally.

The delivery system 2000 further comprises an inner sheath 2014positioned concentrically around at least a distal portion of the pushershaft 2010. The inner sheath 2014 is axially slidable relative to thepusher shaft 2010 between a delivery position (see FIG. 55) and aretracted position (see FIG. 50). In the delivery position, a distal endportion 2016 of the inner sheath 2014 is positioned distal to a distalend, or pusher tip 2018, of the pusher shaft 2010. In the deliveryposition, the distal end portion 2016 of the inner sheath 2014 forms aninner cavity that can contain a compressed prosthetic valve 100. In theretracted position (see FIG. 50), the distal end 2017 of the innersheath 2014 is positioned proximal to or aligned axially with the pushertip 2018. As the inner sheath 2014 moves from the delivery positiontoward the retracted position (either by retracting the inner sheath2014 proximally relative to the pusher shaft 2010 or advancing thepusher shaft distally relative to the inner sheath), the pusher tip 2018can force the prosthetic valve 100 out of the distal end portion 2016 ofthe inner sheath.

As shown in FIG. 50, the inner sheath 2014 comprises one or morelongitudinally disposed slots 2028 extending proximally from a distalend 2017 of the inner sheath. These slots 2028 can allow ventricularanchors 126 of a prosthetic valve 100 contained within the inner sheath2014 to extend radially outward from the compressed main body of theprosthetic valve while the main body is retained in the compressed statewithin the inner sheath. In the embodiment shown in FIG. 50, two slots2028 are shown oriented on diametrically opposed sides of a longitudinalcentral axis of the inner sheath 2014. This embodiment corresponds tothe prosthetic valve 100, which comprises two opposed ventricularanchors 126. In other embodiments, the inner sheath 2014 can comprise adifferent number of slots 2028, for example four slots, that correspondto the number and location of ventricular anchors on a selectedprosthetic valve. In some embodiments, such as shown in FIG. 50, theproximal end portion 2020 of the each slot 2028 comprises a roundedopening that has a greater angular width than the rest of the slot.

A break-away, or frangible, retaining band 2022 can be positioned aroundthe distal end portion 2016 of the inner sheath 2014, as shown in FIG.50. The band 2022 can help retain the distal end portion 2016 of theinner sheath 2014 from splaying apart from the force of a compressedprosthetic valve 100 contained within the inner sheath 2014. The band2022 comprises a proximal edge 2024 that can comprise at least one notch2026 located over a slot 2028 in the inner sheath 2014. The band 2022can comprise a frangible material and can be configured to tear or breakapart at the notch location when a sufficient axial force is applied atthe notch 2026. In use, the band 2022 is configured to break at notches2026 under the force of the ventricular anchors 126 of the valve 100 asit is deployed from the inner sheath 2014, as further described below.

An outer sheath 2036 is positioned concentrically around a portion ofthe inner sheath 2014 and is slidable axially relative to the innersheath. The outer sheath 2036 can be positioned to cover at least aportion of the distal end portion 2016 of the inner sheath 2014. In sucha covered position, such as shown in FIG. 55, the ventricular anchorscan be contained between the inner and outer sheath. The outer sheath2036 is in this covered position while the loaded delivery system 2000is inserted through the body and into the left ventricle 6. The outersheath 2036 can be retracted proximally relative to the sheath 2014 touncover the slots 2028 and allow the ventricular anchors 126 to springoutward through the slots in the inner sheath 2014 during deployment.Alternatively, the inner sheath 2014 can be advanced distally relativeto the outer sheath 2036 to uncover the slots 2028.

With reference to FIG. 51, the handle portion 2002 of the deliverysystem 2000 can comprise components that facilitate sliding the innersheath 2014 and the outer sheath 2036 back and forth along theirrespective ranges of axial movement to load, deliver, and deploy theprosthetic valve 100. An outer sheath grip 2052 can be attached to theproximal end of the outer sheath 2036. A physician can grasp the outersheath grip 2052 and push or pull the outer sheath 2036 proximally ordistally relative to the rest of the delivery system 2000. The outersheath can also be mounted on a lead screw (not shown). The handleportion 2002 of the delivery system 2000 can further comprise a housing2054 that provides a hand grip or handle for the physician to hold thedelivery system 2000 steady while she uses the other hand to actuate thesheaths. A sliding lead screw 2056 can be fixed (e.g., bonded,mechanically locked, etc.) to a proximal end portion 2058 of the innersheath 2014 and be positioned within the housing 2054. The lead screw2056 can be fixed rotationally relative to the housing 2054 and can beconstrained to an axial sliding range within the housing. A rotatablesleeve 2060 can be positioned concentrically between the outer housing2054 and the inner lead screw 2056 and can comprise a proximal knobportion 2062 that extends free of the housing 2054 to provide a handgrip for the physician to rotate the rotatable sleeve 2060. Therotatable sleeve 2060 can be free to rotate relative to the housing2054, but be fixed axially relative to the housing. The lead screw 2056can comprise an outer helical groove 2064 that interacts with inwardlyprojecting ridges 2066 on the rotatable sleeve 2060 such that when theknob 2062 is rotated relative to the lead screw 2056 and the housing2054, the ridges 2066 cause the lead screw 2056 to slide axially,thereby causing the inner sheath 2014 to also slide axially. Thus, thephysician can move the inner sheath 2014 proximally by rotating the knob2062 one direction relative to the housing 2054 and distally by rotatingthe knob the opposite direction relative to the housing. The housing2054 can be fixed relative to the pusher shaft 2010 such that when theknob 2062 is rotated relative to the housing, the lead screw 2056 andthe inner sheath 2014 slide axially together relative to the pushershaft 2010 and the housing 2054.

As shown in FIG. 51, the inner shaft 2006 passes all the way through thehandle portion 2002 of the delivery system 2000 and the pusher shaft2010 can terminate at or near a proximal end cap 2068 of the handleportion 2002. The annular space 2012 between the outer surface of theinner shaft 2006 and the inner surface of the pusher shaft 2010 (seeFIGS. 52 and 53) can be fluidly connected to at least one flushing port2070 in the end cap 2068 of the handle portion 2002. The flushing port2070 can provide access to inject fluid into the annular space 2012and/or allow fluid to escape from the annular space.

As shown in FIG. 49, a nose cone 2030 can be attached to the distal endof the inner shaft 2006. The nose cone 2030 can be tapered from aproximal base 2034 to a distal apex 2032. The base 2034 can have adiameter about equal to the diameter of the outer sheath 2036. The nosecone 2030 can be retracted proximally, by sliding the inner shaft 2006proximally relative to the rest of the delivery system 2000, to mateagainst the distal end of the outer sheath 2036 and/or the inner sheath2014 to further contain the compressed prosthetic valve 100, as shown inFIG. 55. The nose cone 2030 can also be moved distally away from thesheaths to provide space for the prosthetic valve 100 to be loadedand/or deployed. During insertion of the delivery system 2000 throughthe body, the tapered nose cone 2030 can act as a wedge to guide theinsertion portion 2004 of the delivery system 2000 into the body andprovides an atraumatic tip to minimize trauma to surrounding tissue asthe delivery system is advanced through the body.

To load the prosthetic valve 100 into the delivery system 2000, the nosecone 2030 must be moved distally away from the sheaths and the innersheath 2014 must be advanced distally to the delivery position, as shownin FIG. 54 (without retaining band 2022). The outer sheath 2036 can beretracted to expose the slots 2028 in the inner sheath 2014. Theprosthetic valve 100 is then positioned between the nose cone 2030 andthe inner sheath 2014 and around the inner shaft 2006. The prostheticvalve 100 is then compressed to the compressed state and slid into theinner sheath 2014 such that the proximal, or lower, end of theprosthetic valve is adjacent to or contacting the pusher tip, as shownin FIG. 56. A loading cone or equivalent mechanism can be used to insertthe valve 100 into the inner sheath 2014. In embodiments of theprosthetic valve 100 comprising a pusher member 204, such as in FIG. 25,the bottom end 206 of the pusher member 204 can contact the pusher tip2018, as shown in FIG. 56. The ventricular anchors 126 can be allowed toextend out through the rounded proximal end portions 2020 of therespective slots 2028, as shown in FIG. 54. The proximal end portion2020 of each slot can have sufficient angular width to allow the two endportions of the ventricular anchor 126 to reside side-by-side within theslot, which can cause the intermediate portion of the ventricular anchorto assume a desired shape for implanting behind the leaflets 10, 12. Thebreak-away retaining band 2022 can be placed around the distal endportion of the inner sheath 2014 such that each notch 2026 in the band2022 is located over a respective slot, as shown in FIG. 50. The outersheath 2036 is then advanced distally to cover the slots 2028, as shownin FIG. 55, thereby compressing the ventricular anchors 126 andconstraining the ventricular anchors within the outer sheath 2036.Alternatively, the prosthetic valve can be inserted into the innersheath 2014 while the outer sheath 2036 is covering the slots 2028, suchthat the ventricular anchors 126 are positioned in the slots, but cannotextend out of the slots. The ventricular anchors 126 can also beconstrained between the outer surface of the inner sheath 2014 and innersurface of the outer sheath 2036. In any case, the ventricular anchors126 are free to spring radially outward once the outer sheath 2036 isretracted. After the prosthetic valve 100 is within the inner sheath2014, the inner shaft 2006 can be retracted to pull the nose cone 2030against the distal end of the inner sheath 2014 and/or the outer sheath2036, as shown in FIG. 55. With the prosthetic valve 100 within theinner shaft 2006, the nose cone 2030 retracted and the outer sheath 2036constraining the ventricular anchors 126, the delivery system 2000 is inthe loaded configuration and ready for insertion into the body.

In the loaded configuration shown in FIG. 55, the loaded delivery system2000 can be inserted, nose cone 2030 first, through heart apex 38 intothe left ventricle 6 and positioned near the mitral valve region fordeployment. An introducer sheath (not shown) can be initially insertedthrough an incision in the heart to provide a port for introducing thedelivery system 2000 into the heart. In addition, the delivery system2000 can be advanced over a conventional guide wire (not shown) that isadvanced into the heart ahead of the delivery system 2000. The grip 2052can then be moved proximally relative to the rest of the delivery systemto retract the outer sheath 2036 relative to the inner sheath 2014 andallow the ventricular anchors 126 to spring outwardly away from theinner sheath 2014, as shown in FIGS. 56 and 57, such that theventricular anchors extend through the rounded proximal end portion 2020of the slots 2028. The delivery system desirably is orientedrotationally such that each ventricular anchor 126 is positioned betweensets of chordate tendineae 16 attached to one of the native mitral valveleaflets 10, 12. Next, the delivery system 2000 can be advanced atriallysuch that the nose cone 2030 enters the native mitral valve orifice andthe protruding ventricular anchors 126 move between respective leaflets10, 12 and the ventricular walls 20, as shown in FIG. 58. Then, whileholding a housing 2054 of the delivery system 2000 steady, the physiciancan rotate the knob 2062 of the rotatable sleeve 2060 relative to thehousing to retract the inner sheath 2014 proximally. The pusher tip 2018remains stationary while the inner sheath 2014 retracts, thereby leavingthe compressed prosthetic valve 100 in the same axial location as it isuncovered and deployed from the inner sheath 2014. Alternatively, theinner sheath 2014 can be held stationary while the pusher tip 2060 ismoved distally to push the valve 100 out of the inner sheath 2014. Whilethe inner sheath 2014 is being retracted relative to the pusher tip2018, the pusher tip can exert an axial force in the distal directionupon the proximal, or lowermost, surface of the prosthetic valve 100. Inembodiments of the prosthetic valve having a pusher member 204, thepusher member 204 can direct this axial force directly to the main body122 and prevent direct contact between the pusher tip 2018 and theventricular anchor 126 to reduce the risk of damage to the ventricularanchors.

When the inner sheath 2014 is retracted relative to the prosthetic valve100, the distal, or upper, portion of the prosthetic valve comprisingthe downwardly folded atrial sealing member 124 is uncovered first. Withreference to FIGS. 59 and 60, when the inner sheath 2014 has beenretracted beyond the outer rim of the atrial sealing member 124 of theprosthetic valve 100, the atrial sealing member can spring radiallyoutward away from the main body 122, pivoting about the distal end ofthe main body.

As the inner sheath 2014 is retracted relative to the prosthetic valve100, the end portions of the ventricular anchors 126 passing through therounded proximal end portion 2020 of the slots 2028 are forced throughthe narrower distal portions of the slots 2028 toward the retaining band2022, as shown in FIGS. 59 and 60. The end portions of the ventricularanchors are initially side-by-side in the wider proximal end portion2020 of the slot. When forced into the narrower portion of a slot 2028,the two end portions of each ventricular anchor 126 can be radiallyoverlapping, or oriented one on top of the other, as opposed toside-by-side. In other embodiments, the slots 2028 can be wider suchthat the two end portions of the ventricular anchor 126 can move aboutthe slots 2028 side-by-side. As the ventricular anchor 126 moves towardthe distal end of a slot 2028, the ventricular anchor can contact thenotch 2026 in the retaining band 2022, as shown in FIG. 60, and can cutthe band 2022 or otherwise cause the band to tear or split apart at thenotched location, as shown in FIG. 61. When the inner sheath 2014 isretracted beyond the proximal, or lower, end of the prosthetic valve100, the compressed body of the prosthetic valve can resilientlyself-expand to the expanded state, as shown in FIG. 61. As theprosthetic valve expands, the gaps between the ventricular anchors 126and the outer surface of the main body 122 decreases, capturing theleaflets 10, 12 between the ventricular anchors 126 and the main body122, as shown in FIGS. 23 and 62. The expansion of the main body 122 ofthe prosthetic valve 100 can force open the native mitral leaflets 10,12, holding the native mitral valve 2 in an open position. Theprosthetic valve 100 can then replace the functionality of the nativemitral valve 2. After the prosthetic valve 100 is expanded, the innershaft 2006 of the delivery system can be retracted, pulling the nosecone 2030 back through the prosthetic valve, and the whole deliverysystem 2000 can be retracted out of the body.

In some embodiments, the delivery system 2000 can be guided in and/orout of the body using a guide wire (not shown). The guide wire can beinserted into the heart and through the native mitral orifice, and thena proximal end of the guidewire can be threaded through the lumen 2008of the inner shaft 2006. The delivery system 2000 can then be insertedthrough the body using the guidewire to direct the path of the deliverysystem.

Atrial Approaches

The prosthetic valve 100 can alternatively be delivered to the nativemitral valve region from the left atrium 4. Referring to FIGS. 63-67,one approach for delivering the prosthetic valve from the atrial side ofthe mitral valve region utilizes a delivery catheter 2100. Theprosthetic valve 100 is first crimped from the expanded state to theradially compressed state and loaded into a primary sheath 2102, andoptionally also a secondary sheath, at the distal end portion of thedelivery catheter 2100, as shown in FIG. 63. The delivery catheter 2100is used to guide the prosthetic valve 100 through the body and into theleft atrium 4. The prosthetic valve 100 is oriented within the sheath2102 such that the outflow end 112 of the prosthetic valve 100 (the endsupporting the ventricular anchors 126) is closest to the distal end ofthe sheath and thus enters the left atrium 4 first and the inflow end110 (the atrial sealing member 124) of the prosthetic valve enters last.The sheath 2102 can then be inserted into the left atrium 4 in variousmanners, one example being the transatrial approach shown in FIG. 66,and another example being the transeptal approach shown in FIG. 67. Whenthe delivery catheter 2100 is used to access the heart via the patient'svasculature, such as shown in FIG. 67, the catheter 2100 can comprise aflexible, steerable catheter.

Once in the left atrium 4, the distal end 2104 of the primary sheath2102 can be moved across the mitral annulus 8 such that the ventricularanchors 126 are positioned beyond the mitral leaflets 10, 12 prior todeploying the ventricular anchors from the sheath.

The prosthetic valve 100 can then be partially expelled from of thedistal end 2104 of the primary sheath 2102 using a rigid pusher shaft2106 (see FIG. 64) that is positioned within the sheath 2102 and canslide axially relative to the sheath. When the sheath 2102 is retractedproximally relative to the pusher shaft 2106 and the prosthetic valve100, the pusher shaft 2106 urges the prosthetic valve distally out ofthe sheath 2102, as shown in FIG. 64. Alternatively, the pusher shaft2106 can be moved distally while the sheath 2102 is held in place,thereby pushing the prosthetic valve 100 distally out of the sheath.

When the primary sheath 2102 is inserted across the mitral annulus 8 andpast the lower ends of the leaflets 10, 12, the prosthetic valve 100 canbe partially expelled to free the ventricular anchors 126, as shown inFIG. 64. The freed ventricular anchors 126 can spring outwardly whenthey are freed from the sheath 2102. Optionally, the sheath 2102 canthen be slid back over the exposed portion of the main body 122, suchthat only the ventricular anchors are showing, as shown in FIG. 65. Toaccomplish this step, the atrial end of the frame can comprise features(not shown), such as mechanical locking features, for releasablyattaching the prosthetic valve 100 to the pusher shaft 2106, such thatthe pusher shaft can pull the prosthetic valve back into the sheath2102. The sheath 2102 and the prosthetic valve 100 are then retractedatrially, proximally, such that the outwardly protruding ventricularanchors 126 move between respective leaflets 10, 12, and the ventricularwalls 20, as shown in FIGS. 66-68. In other embodiments, such as thoseshown in FIGS. 44 and 45, the ventricular anchors can elasticallydeflect upward or bend around respective leaflets 10, 12 when theventricular anchors are freed from the sheath 2102.

Optionally, the delivery catheter 2100 can also include a secondarysheath (not shown) within the outer sheath 2102 and can contain thepusher shaft 2106, the atrial sealing member 124 and the main body 122of the frame, but not the anchors 126. In the position shown in FIG. 63,the distal end of the secondary sheath can be positioned between theanchors 126 and the main body 122. As the outer primary sheath 2102 isretracted, as in FIG. 64, the secondary sheath can remain in a positioncompressing the main body 122 of the frame while the anchors 126 arefreed to extend outward. Because the secondary sheath remains coveringand compressing the main body 122, there is no need recover the mainbody with the primary sheath 2102, as in FIG. 65. Instead, theprosthetic valve 100 is moved proximally by moving the secondary sheathand pusher shaft proximally in unison. Then, to expel the prostheticvalve 100 from the secondary sheath, the secondary sheath is retractedproximally relative to the pusher shaft 2106.

After the ventricular anchors 126 are positioned behind the leaflets 10,12 and the remaining portion of the prosthetic valve 100 is expelledfrom the primary sheath 2102, the prosthetic valve 100 can expand to itsfunctional size, as shown in FIGS. 62 and 69, thereby capturing theleaflets 10, 12 between the ventricular anchors 126 and the main body122. Once the prosthetic valve 100 is implanted, the delivery catheter2100 can be retracted back out of the body.

In alternative prosthetic valve embodiments, the main body and theatrial sealing member of the frame can be plastically expandable and canbe expanded by a balloon of a balloon catheter (not shown) when theprosthetic valve is positioned at the desired location. The ventricularanchors in such an embodiment can exhibit a desired amount of elasticityto assist in positioning the leaflets 10, 12 between the ventricularanchors and the main body during deployment. Once the prosthetic valveis fully expanded, the balloon can be retracted through the expandedprosthetic valve and out of the body.

Mitral Regurgitation Reduction

Mitral regurgitation (MR) occurs when the native mitral valve fails toclose properly and blood flows into the left atrium from the leftventricle during the systole phase of heart contraction. MR is the mostcommon form of valvular heart disease. MR has different causes, such asleaflet prolapse, dysfunctional papillary muscles and/or stretching ofthe mitral valve annulus resulting from dilation of the left ventricle.MR at a central portion of the leaflets can be referred to as centraljet MR and MR nearer to one commissure of the leaflets can be referredto as eccentric jet MR.

Rather than completely replacing the native mitral valve, another way totreat MR is by positioning a prosthetic spacer between the leaflets thatdecreases the regurgitant orifice area, allowing the mitral valve tofunction with little or no regurgitation, while minimizing impact to thenative valve and left ventricle function and to the surrounding tissue.Additional information regarding treatment of MR can be found in U.S.Pat. No. 7,704,277 and U.S. Publication No. 2006/0241745 A1, both ofwhich are incorporated by reference herein.

FIG. 71 shows an exemplary prosthetic spacer embodiment 3000 with whicha spacer, or other body, can be suspended or “floated” between theleaflets using anchoring concepts described herein. The prostheticspacer 3000 can comprise a frame 3002 and spacer body 3004. The spacerbody 3004 can comprise polyurethane, foam, and/or other suitablematerial(s) and can optionally be coated with Teflon and/or othersuitable material(s). The spacer body 3004 can comprise a crescent shapethat conforms to the crescent shaped juncture between the anteriorleaflet 10 and the posterior leaflet 12 (see FIGS. 4A and 4B), or thespacer body can comprise other suitable shapes, such as an ellipse,circle, hourglass, etc. Depending on the shape of the spacer body 3004and the positioning of the spacer body relative to the native structure,embodiments of the prosthetic spacer 3000 can help treat central jet MR,eccentric jet MR, or both.

Furthermore, the spacer body 3004 can comprise a minimal transversecross-sectional area and tapered edges. This shape can reduce diastolicforces from blood flowing through the mitral valve from the left atriumto the left ventricle. This shape can also reduce systolic forces on thespacer body 3004 when the native valve is closed around the spacer bodyand naturally place a larger portion of the systolic forces on thenative leaflets and chordae. The shape of the spacer body 3004 cantherefore reduce the forces transferred to the native valve tissue atanchor engagement locations, which can reduce the likelihood ofperforation and erosion at the engagement locations and rupture of thenative chordae that support the leaflets. The overall minimal size ofthe prosthetic spacer 3000 can further provide an opportunity todecrease the required cross-sectional size of a delivery system,allowing for delivery via narrower vasculature and/or less invasiveincisions in the body and heart.

The frame 3002 can be made of a strong, flexible material, such asNitinol. As shown in FIG. 71, the frame 3002 can comprise a frame body3006, an anterior ventricular anchor 3008, a posterior ventricularanchor 3010, an anterior atrial anchor 3012 and a posterior atrialanchor 3014. The frame body 3006 can comprise a generally longitudinalcolumn extending through the spacer body 3004. Various embodiments ofthe frame body 3006 are described in detail below.

The frame 3002 can further comprise one or more spacer expanders 3024extending laterally from the frame body 3006 through the spacer body3004. The expanders 3024 can resiliently expand away from the frame bodyand assist in the expansion of the spacer body 3004 during deployment.In some embodiments, the spacer expanders 3024 can be rectangularcut-out portions of a cylindrical frame body 3006, as shown in FIG. 71,that are bent radially away from the frame body.

The anterior ventricular anchor 3008 is configured to extend from theventricular end of the frame body 3006, around the A2 edge of theanterior leaflet 10 and extend upward behind the leaflet to a locationon the ventricular surface of the mitral annulus 8 and/or the annulusconnection portion of the anterior leaflet, while the anterior atrialanchor 3012 is configured to extend radially from the atrial end of theframe body 3006 to a location on the atrial surface of the mitralannulus 8 opposite the anterior ventricular anchor 3008. Similarly, theposterior ventricular anchor 3010 is configured to extend from theventricular end of the frame body 3006, around the P2 edge of theposterior leaflet 12 and extend upward behind the leaflet to a locationon the ventricular surface of the mitral annulus 8 and/or the annulusconnection portion of the posterior leaflet, while the posterior atrialanchor 3014 is configured to extend radially from the atrial end of theframe body 3006 to a location on the atrial surface of the mitralannulus 8 opposite the posterior ventricular anchor 3010.

The ventricular anchors 3008, 3010 and the atrial anchors 3012, 3014 cancomprise broad engagement portions 3016, 3018, 3020 and 3022,respectively, that can be configured to compress the mitral annulus 8and/or annulus connection portions of the leaflets 10, 12 to retain theprosthetic spacer 3000 from movement in both the atrial and ventriculardirections. The broad engagement portions can provide a greater area ofcontact between the anchors and the native tissue to distribute the loadand reduce the likelihood of damaging the native tissue, such asperforation or erosion at the engagement location. The ventricularanchors 3008, 3010 in the illustrated configuration loop around thenative leaflets 10, 12 and do not compress the native leaflets againstthe outer surface of the spacer body 3004, allowing the native leafletsto naturally open and close around the spacer body 3004.

As shown in FIG. 74, the mitral annulus 8 is generally kidney shapedsuch that the anterior-posterior dimension is referred to as the minordimension of the annulus. Because the prosthetic spacer 3000 can anchorat the anterior and posterior regions of the native mitral valve 2, theprosthetic spacer can be sized according to the minor dimension of theannulus 8. Echo and CT measuring of the minor dimension of the mitralannulus 8 are exemplary methods of sizing the prosthetic spacer 3000.

FIGS. 75-79 illustrate an exemplary method for delivering the prostheticspacer 3000 to the native mitral valve region of the heart. Theprosthetic spacer 3000 can be delivered into the heart using a deliverysystem comprising an outer sheath 3030 and inner torque shaft 3032. Theprosthetic spacer 3000 is compressed and loaded into a distal end of theouter sheath 3030 with the atrial anchors 3012, 3014 loaded first. Asshown in FIG. 75, the atrial anchors are resiliently extended proximallyand the ventricular anchors 3008, 3010 are resiliently extended distallysuch that the prosthetic spacer 3000 assumes a sufficiently narrowcross-sectional area to fit within the lumen of the outer sheath 3030.Within the outer sheath 3030, the prosthetic spacer 3000 is positionedsuch that the atrial end of the frame body 3006 abuts the distal end ofthe torque shaft 3032, the atrial anchors 3012, 3014 are between thetorque shaft and the inner wall of the outer shaft, the compressedspacer 3004 abuts the inner wall of the outer sheath, and the distalends of the ventricular anchors 3008, 3010 are adjacent to the distalopening of the outer sheath. The torque shaft 3032 can be releasablycoupled to the atrial end of the prosthetic spacer 3000, such as at theproximal end of the frame body 3006.

Once loaded, the delivery system can be introduced into the left atrium4, such as via the atrial septum 30, and the distal end of the outersheath 3030 can be passed through the native mitral valve 2 and into theleft ventricle 6, as shown in FIG. 75.

Next, the outer sheath 3030 can be retracted relative to the torqueshaft 3032 to expel the ventricular anchors 3008, 3010 from the distalopening of the outer sheath. At this point, the torque shaft 3032 can berotated to rotate the prosthetic spacer 3000 within the outer sheath3030 (or optionally, the torque shaft and the outer sheath can both berotated) as needed to align the ventricular anchors with the A2/P2aspects of the native valve 2. The releasable attachment between thetorque shaft 3032 and the prosthetic spacer 3000 can be sufficient totransfer torque from the torque shaft to the prosthetic in order torotate the prosthetic as needed. The ventricular anchors 3008, 3010 canbe pre-formed such that, as they are gradually expelled from the outersheath 3030, they begin to curl apart from each other and around theA2/P2 regions of the leaflets. This curling movement can be desirable toavoid entanglement with the ventricular walls. When the outer sheath3030 is retracted to the ventricular end of the frame body 3006, asshown in FIG. 76, the ventricular anchors 3008, 3010 are fully expelledfrom the outer sheath and positioned behind the leaflets. The entiredelivery system and prosthetic can them be moved proximally until theengagement portions 3016, 3018 of the ventricular anchors abut theventricular side of the mitral annulus 8 and/or the annulus connectionportions of the leaflets 10, 12.

Next, the outer sheath 3030 can be further retracted to relative to thetorque shaft 3032 such that the distal end of the outer sheath is evenwith the atrial end of the frame body 3006, as shown in FIG. 77, whichallows the compressed spacer expanders 3024 and the compressed spacerbody, or other body, 3004 to resiliently self-expand radially outward tothe fully expanded, functional state. Note that the spacer body 3004expands mostly in a direction perpendicular to the minor dimension ofthe annulus, or toward the commissures 36 (see FIG. 74). In someembodiments, the spacer body 3004 can unfold or unfurl from thecompressed state to the expanded state and in some embodiments thespacer body can be inflated, such as with saline or with an epoxy thathardens over time.

Once the spacer body is expanded within the valve, as shown in FIG. 77,hemodynamic evaluation of the spacer can be performed to assess theeffectiveness of the prosthetic spacer 3000 in reducing MR. Depending onthe result of the evaluation, deployment can continue or the prostheticspacer 3000 can be recovered, retracted and/or repositioned fordeployment.

From the position shown in FIG. 77, the outer sheath 3030 can beadvanced back over the spacer body 3004 (by advancing the outer sheath3030 relative to the torque shaft 3032), causing the spacer body tore-compress, as shown in FIG. 76. In some embodiments, the ventricularanchors are not recoverable, though in some embodiments the ventricularanchors can be sufficiently pliable to be re-straightened and recovered,in which case then entire delivery process can be reversed andrestarted. From the position shown in FIG. 76, the delivery system canbe repositioned and the spacer body 3004 can be redeployed andreassessed.

Once the ventricular anchors 3008, 3010 and the spacer body 3004 areacceptably deployed, the outer sheath 3030 can be further retractedrelative to the prosthetic spacer 3000 and the torque shaft 3032 toexpel the atrial anchors 3012, 3014 from the outer sheath, as shown inFIG. 78. Once fully expelled, the atrial anchors resiliently curl intotheir final deployment position shown in FIG. 78 with their engagementportions 3020, 3022 pressed against the atrial side of the annulus 8and/or the annulus connection portions of the leaflets 10, 12 oppositethe engagement portions 3016, 3018, respectively, of the ventricularanchors, thereby compressing the annulus and/or the annulus connectionportions of the leaflets at the A2 and P2 regions to retain theprosthetic spacer 3000 within the native mitral valve region 2.

Once the atrial anchors 3012, 3014 are deployed, the torque shaft 3032can be released from the atrial end of the frame body 3006. The deliverysystem can then be retracted back out of the body, leaving theprosthetic spacer 3000 implanted, as shown in FIG. 79.

In some embodiments, the spacer body 3004 can comprise a valve structure3040, such the embodiments shown in FIGS. 80 and 82. The valve structure3040 can function in conjunction with the native mitral valve 2 toregulate blood flow between the left atrium 4 and the left ventricle 6.For example, the valve structure 3040 can be positioned between thenative leaflets such that the native leaflets close around the outsideof the valve structure such that some blood flows through the valvestructure while other blood flows between the outside of the valvestructure and the native leaflets. The valve structure 3040 can comprisea three-leaflet configuration, such as is described herein withreference to the valve structure 104 and shown in FIGS. 5-7.

In some embodiments, the frame body 3006 can comprise a cylinder, whichcan optionally comprise solid-walled tube, such as in FIGS. 71-74, amesh-like wire lattice 3046, such as in FIG. 82, or other cylindricalconfigurations. With reference to FIGS. 71-75, the frame body 3006 andoptionally one or more of the anchors can be formed from a solid-walledtube, such as of Nitinol, wherein the atrial anchors are formed, such asby laser cutting, from one portion of the tube and the ventricularanchors are formed from a second portion of the tube and the frame bodyis formed from a portion of the tube between the first and secondportions. The anchors can then be formed, such as by heat treatment, toa desired implantation configuration. In such embodiments, the anchorsand the frame body can be a unibody, or monolithic, structure.

In other embodiments, the frame body 3006 can comprise a spring-likehelically coiled wire column 3050, as shown in FIG. 83. Such a coiledcolumn 3050 can be made from wire having a round or rectangularcross-section and can comprise a resiliently flexible material, such asNitinol, providing lateral flexibility for conforming to the nativevalve structure while maintaining longitudinal column stiffness fordelivery. In some of these embodiments, the frame body 3006 can comprisea quadrahelical coil of four wires having four atrial ends that extendto form the atrial anchors 3012, 3014 and four ventricular ends thatextend to form the four ventricular anchors 3008, 3010.

In other embodiments, the frame body 3006 can comprise a plurality oflongitudinal members (not shown). In one such example, the frame body3006 can comprise four longitudinal members: two longitudinal membersthat extend to form the anterior anchors 3012, 3014 and two longitudinalmembers that extend to from the posterior anchors 3008, 3010.

In other embodiments, the frame body 3006 can comprise a zig-zag cutpattern 3050 along the longitudinal direction of the body, as shown inFIG. 81, that can also provide lateral flexibility while maintainingcolumn strength.

In some embodiments, the prosthetic spacer 3000 can have additionalanchors. In some embodiment (not shown), the prosthetic spacer 3000 canhave three pairs of anchors: one pair of anchors centered around theposterior leaflet 12, such as the posterior anchors 3010 and 3014described above, and one pair of anchors at each commissure 36 betweenthe native leaflets 10, 12. These commissure anchors pairs can similarlycomprise a ventricular anchor and an atrial anchor and can similarlycompress the native annulus 8. In other embodiments, the anterioranchors 3008 and 3012 can also be included as a fourth pair of anchors.Other embodiments can comprise other combinations of these four pairs ofanchors and/or additional anchors.

In addition to filling the regurgitant orifice area and blocking bloodfrom flowing toward the left atrium, the prosthetic spacer 3000 can alsoadd tension to the chordae tendinae to prevent further enlargement ofthe left ventricle and prevent further dilation of the mitral valveannulus.

Anchoring Beneath the Mitral Valve Commissures

Some embodiments of prosthetic devices comprising ventricular anchors,including both prosthetic valves and prosthetic spacers, can beconfigured such that the ventricular anchors anchor beneath thecommissures 36 of the native mitral valve 2 instead of, or in additionto, anchoring behind the A2/P2 regions of the native mitral leaflets 10,12. FIGS. 84-87 show exemplary prosthetic device embodiments thatcomprise ventricular anchors that anchor beneath the two commissures 36of the native mitral valve 2, and related delivery methods. Thesecommissure-anchoring concepts are primarily for use with prostheticvalves, but can be used with other prosthetic devices, includingprosthetic spacers.

As shown in FIGS. 3, 4 and 88, the commissures 36 are the areas of thenative mitral valve 2 where the anterior leaflet 10 and the posteriorleaflet 12 are joined. Portions 39 of the native mitral annulus 8adjacent to each commissure 36, as shown in FIG. 88, can be relativelythicker and/or stronger than the portions of the mitral annulus 8adjacent to the intermediate portions of the leaflets A2/P2, providing arigid, stable location to anchor a prosthetic apparatus. These annulusregions 39 can comprise tough, fibrous tissue that can take a greaterload than the native leaflet tissue, and can form a natural concavesurface, or cavity.

FIGS. 84 and 85 show an exemplary prosthetic apparatus 4000 beingimplanted at the native mitral valve region 2 by positioning aventricular anchor 4002 at one of the cavities 39. The prostheticapparatus 4000 can be a prosthetic valve having a leaflet structure or aspacer device having a spacer body 3004 for reducing MR. The chordaetendinae 16 attach to the leaflets 10, 12 adjacent to the commissures36, which can present an obstacle in positioning ventricular anchors inthe cavities 39 behind the chordae. It is possible, however, to deliveranchors, such as anchor 4002, around the chordae 16 to reach thecavities 39. Positioning engagement portions, such as the engagementportion 4004, of the ventricular anchors behind the chordae 16 in thesenatural cavities 39 can be desirable for retaining a prostheticapparatus at the native mitral valve region 2. However, to avoidentanglement with and/or damage to the native chordae 16, it can bedesirable to first guide the engagement portions of the anchorsvertically behind the leaflets 10, 12 at the A2/P2 regions, between thechordae 16 from the postero-medial papillary muscle 22 and the chordae16 from the antero-lateral papillary muscle 24, as shown in FIG. 84, anthen move or rotate the engagement portions of the anchors horizontallyaround behind the chordae 16 toward the commissure cavities 39, as shownin FIG. 85.

In some such methods, the ventricular anchors are first deployed behindthe A2/P2 regions of the leaflets and then the entire prostheticapparatus is rotated or twisted to move the engagement portions of theanchors horizontally toward the cavities 39, as shown in FIGS. 84 and85. For example, a first anchor deployed behind the anterior leaflet 10can move toward one of the cavities 39 while a second anchor deployedbehind the posterior leaflet 12 can move toward the other cavity 39.This method can also be referred to as a “screw method” because theentire prosthetic is rotated to engage the anchors with the nativetissue.

As shown in FIGS. 84 and 85, a prosthetic apparatus 4000 comprisingbent, curved, hooked, or generally “L” shaped, anchors 4002 can be usedwith the screw method. The “L” shaped anchors 4002 can comprise a legportion 4006 the extends vertically upward from the body of theapparatus 4000, a knee portion 4008, and a foot portion 4010 extendinghorizontally from the knee portion and terminating in the engagementportion 4004. In some of these embodiments, the “L” shaped anchor 4002can comprise a looped wire that attaches to the body of the apparatus4000 at two locations, such that the wire forms a pair of leg portions4006, a pair of knee portions 4008 and a pair of foot portions 4010. Inother embodiments, the anchor 4002 can have other similar shapes, suchas a more arced shape, rather than the right angle shape shown in FIG.84. During delivery into the heart, the foot portion 4010 can be curledor wrapped around the outer surface of the body of the apparatus 4000.

As shown in FIG. 84, in order to move the foot portion 4010 verticallybehind the leaflet 10 without entanglement with the chordae, the legportion 4006 can be positioned slightly off center from the A2 region,closer to the chordae opposite the cavity 39 of desired delivery. Asshown in FIG. 84, the leg portion 4006 is positioned to the right suchthat the foot portion 4010 can pass between the chordae 16.

After the foot portion 4010 clears the chordae 16 and is positionedbehind the leaflet, the apparatus 4000 can be rotated to move theengagement portion 4004 horizontally into the cavity 39, as shown inFIG. 85. Note that in FIG. 85 the leg portion 4006 can end up positionedat the A2/P2 region between the chordae 16 to avoid interference withthe chordae.

While FIGS. 84 and 85 show a single anchor 4002, both an anterior and aposterior anchor can be delivery in symmetrical manners on oppositesides of the native valve 2, one being anchored at each cavity 39. Thefeet 4010 of the two anchors 4002 can point in opposite directions, suchthat the twisting motion shown in FIG. 85 can move them simultaneouslyto the two cavities 39. During delivery of two anchor embodiments, thetwo foot portions 4010 can wrap around the outer surface of the body ofthe apparatus 4000 such that the two foot portions 4010 overlap oneanother.

In similar embodiments, the anchors 4002 can comprise a paddle shape(see FIG. 37 for example) having two foot portions 4010 extending inopposite directions. While more difficult to move between the chordae,these paddle shaped anchors can allow the apparatus 4000 to be rotatedin either direction to engage one of the foot portions 4010 at a cavity39. In some embodiments, the paddle shaped anchors can be wide enoughsuch that one foot portion 4010 can be positioned at one cavity 39 whilethe other foot portion is positioned at the other cavity.

Because the anchors 4002 each attach to the body of the apparatus 4000at two locations, the anchors can spread apart from the main body of theapparatus when the main body is compressed, forming a gap to receive aleaflet, as described in detail above with reference to FIGS. 11-22. Insome embodiments, the anchors can separate from the main body when themain body is compressed and either remain separated from the main body,such that the leaflets are not pinched or compressed between the anchorsand the main body of the apparatus, or close against the main bodyduring expansion to engage the leaflets. In some embodiments, the mainbody can move toward the anchors to reduce the gap when then main bodyexpands while maintaining the distance between the foot portions 4010 ofthe opposing anchors.

FIGS. 86 and 87 shown another exemplary prosthetic apparatus 5000 beingimplanted at the native mitral valve region 2 by positioning ventricularanchors 5002 at the cavities 39 and a corresponding method for do so. Inthis embodiment, the apparatus 5000 can comprise a pair of “L” shapedanchors 5002 on each side (only one pair is visible in FIGS. 86 and 87),with each pair comprising one anchor for positioning in one of thecavities 39 and another anchor for positioning in the other cavity. Eachof the anchors can comprise a leg portion 5006 extending vertically fromthe body of the apparatus 5000 to a knee portion 5008, and a footportion 5010 extending horizontally from the knee portion 5008 to anengagement portion 5004. In other embodiments, the anchors 5002 can haveother similar shapes, such as a more arced shape, rather than the angledshape shown in FIG. 86.

Each pair of anchors 5002 can comprise a resiliently flexible material,such as Nitinol, such that they can be pre-flexed and constrained in acocked position for delivery behind the leaflets, as shown in FIG. 86,and then released to resiliently spring apart to move the engagementportions 5004 in opposite directions toward the two cavities 39, asshown in FIG. 87. Any suitable constrainment and release mechanisms canbe used, such as a releasable mechanical lock mechanism. Once released,one anterior anchor and one posterior anchor can be positioned at onecavity 39 from opposite directions, and a second anterior anchor and asecond posterior anchor can be positioned at the other cavity fromopposite directions. Some embodiments can include only one anchor oneach side of the apparatus 5000 that move in opposite directions towardopposite cavities 39 when released.

Because each pair of anchors 5002 are initially constrained together, asshown in FIG. 86, each pair of anchors can act like a single anchorhaving two attachment points to the main body of the apparatus 5000.Thus, the anchor pairs can separate, or expand away, from the main bodywhen the main body is compressed and either remain spaced from the mainbody, such that the leaflets are not pinched or compressed between theanchors and the main body of the apparatus, or close against the mainbody during expansion to engage the leaflets. In some embodiments, themain body can move toward the anchor pairs to reduce the gap when thenmain body expands while maintaining the distance between the footportions 5010 of the opposing anchor pairs.

In the embodiments shown in FIGS. 84-87, the prosthetic apparatus 4000or 5000 can have a main frame body similar to the embodiments shown inFIG. 5, from which the ventricular anchors 4002, 5002 can extend, andcan further comprise one or more atrial anchors, such as an atrialsealing member similar to the atrial sealing member 124 shown in FIG. 5or a plurality of atrial anchors similar to the atrial anchors 3012 and3014 shown in FIG. 71, for example. The atrial anchors can extendradially outward from an atrial end of the prosthetic apparatus andcontact the native tissue opposite the cavities 39 and thereby compressthe tissue between the atrial anchors and the engagement portions 4004,5004 of the ventricular anchors 4002, 5002 to retain the prostheticapparatus at the native mitral valve region. The atrial anchors and theventricular anchors can comprise a broad contact area to distribute theload over a wider area and reduce the likelihood of damaging the nativetissue.

Disclosure from U.S. Provisional Application Nos. 61/266,774 and61/287,099

FIG. 89 shows a prosthetic mitral valve 5118, according to oneembodiment, that comprises a stent, or support frame, 5120 and aplurality of leaflets (not shown) supported by the stent.

As shown in FIGS. 90A and 90B, the mitral valve stent 5120 includes amain stent body comprising a valve portion 5122, an atrial body 5124,and a plurality of clips 5126 coupled to the main stent body. The stent5120 can be made of a wire mesh and can be radially collapsible andexpandable to enable implantation. The wire mesh can include metalstrips or struts arranged in a lattice pattern, as shown in FIGS. 90Aand 90B, but other patterns may be used. FIGS. 91A-91D show one suchalternative embodiment.

As shown in FIGS. 90A and 90B and in FIGS. 91A-D, two or more clips canextend from the ventricular end of the valve body 5122. These clipsfunction to secure the stent 5120 to the anterior and posterior mitralleaflets 5110 and 5112, as shown in FIG. 89. The clips 5126 in theillustrated embodiment are configured to wrap around the ends of theleaflets and extend atrially between the back of the leaflets and theventricular walls 5107. Desirably, the clips are configured to pinch orcompress a leaflet of the native valve between the valve portion 5122 ofthe stent and the clip. The clips 5126 assist in retaining the stent5120 in place against the flow of blood, particularly in the atrialdirection. The clips 5126 and the frustoconical portion 5128 of thestent cooperate to anchor the stent within the mitral annulus 5108.

In some embodiments of the stent 5120, the clips can be finger-likeclips and can extend from only one attachment point on the valve body5122, as shown in FIGS. 92A and 92B. The pre-formed shape of thefinger-like clips 5150 can be curved to facilitate capturing theleaflets 5110, 5112 between the clips and the valve portion of the stentduring implantation. In other embodiments, as shown in FIG. 93, thefinger-like clips 5150 can be pre-formed into curls or coils 5152. Thecoiled shape of the clips 5152 can aid in the capture the leaflets 5110,5112 when the stent is implanted. During delivery of the valve, theclips 5152 can be partially or completely unfurled and retained in thatstate by a delivery sheath. As the stent is advanced from the sheath,the clips are allowed to revert back to their curled shape, capturingthe leaflets between the clips and the stent.

In other embodiments of the stent, the anchors can be pre-formed invarious desired configurations and can be deformed or straightened tofit into a sheath (not shown) during implantation, as shown in theleft-most drawings of FIGS. 94A, 95 and 96. The deformed anchors 5226can elastically regain their pre-formed shape once freed from the sheathto facilitate capturing the leaflets 5110, 5112 between the anchors andthe valve portion 5222 of the stent.

FIGS. 94A and 94B show an embodiment of the stent having curling anchors5290. The curling anchors 5290 can be finger-like—extending from onlyone attachment point on the valve portion 5222. The curling anchors 5290can be pre-formed into curls or coils. The coiled shape of the anchors5290 can aid in the capture the leaflets 5110, 5112 when the device isimplanted. During delivery of the device, the anchors 5290 can bepartially or completely unfurled, or straightened, and retained in thatstate by a delivery sheath. As the device is advanced from the sheath,the curling anchors 5290 are allowed to spring back to their curledshape, capturing the leaflets between the anchors and the valve body5222. In other embodiments, the curling anchors 5290 can extend from twoor more attachment points on the valve portion 5222, rather than beingfinger-like.

In view of the many possible embodiments to which the principlesdisclosed herein may be applied, it should be recognized that theillustrated embodiments are only preferred examples and should not betaken as limiting the scope of the disclosure. Rather, the scope isdefined by the following claims. We therefore claim all that comeswithin the scope and spirit of these claims.

We claim:
 1. A method for implanting a prosthetic valve at a mitralvalve region of a heart, the mitral valve region having a native mitralannulus, the method comprising: delivering to the native mitral annulusa prosthetic valve comprising: a frame having an expanded and acollapsed state, the frame having a longitudinal axis and comprising: amain body having an atrial end and a ventricular end, the main bodydefining inner and outer surfaces; a lower anchoring portion at theventricular end of the main body that comprises a plurality of anchors,each of the anchors having a first end that is attached to the main bodyand a second end that is spaced from the first end; and an upperanchoring portion at the atrial end of the main body that comprises anatrial portion configured to be positioned on an atrial side of thenative mitral annulus, the atrial portion comprising a plurality ofstruts, the atrial portion having a first end that is attached to themain body and a second end that is spaced from the first end; and avalve structure attached to the inner surface of the main body of theframe; wherein when the frame is in the collapsed state, the upper andlower anchoring portions are oriented substantially along thelongitudinal axis of the frame; wherein when the frame transitions fromthe collapsed state to the expanded state, the lower anchoring portiontransitions to a configuration that is no longer oriented substantiallyalong the longitudinal axis of the frame; and wherein the loweranchoring portion is configured to capture tissue at the ventricularside of the native mitral annulus between the lower anchoring portionand the outer surface of the main body as the frame transitions from thecollapsed state to the expanded state; and expanding the frame to anchorthe prosthetic valve at the native mitral annulus.
 2. The methodaccording to claim 1, wherein: the plurality of anchors comprise curlinganchors; and when the frame is in the collapsed state, the curlinganchors are oriented substantially along the longitudinal axis of theframe; and when the frame transitions from the collapsed state to theexpanded state, the curling anchors transition to a configuration thatis no longer oriented substantially along the longitudinal axis of theframe.
 3. The method according to claim 2, wherein the curling anchorseach extend from two or more attachment points on the main body.
 4. Themethod according to claim 2, wherein the curling anchors arefinger-like.
 5. The method according to claim 4, wherein curling anchorseach extend from one attachment point on the main body.
 6. The methodaccording to claim 1, wherein the plurality of anchors comprise curlinganchors; and when the frame is in the collapsed state, the curlinganchors extend in a ventricular direction and are substantiallystraightened; and when the frame transitions from the collapsed state tothe expanded state, the curling anchors transition to a shape in whichthe curling anchor is curled.
 7. The method according to claim 1,wherein the prosthetic valve is delivered to the native mitral annulusvia a delivery sheath.
 8. The method according to claim 1, wherein theprosthetic valve is delivered to the implantation site transatrially,transapically, or via the patient's vasculature.
 9. The method accordingto claim 1, further comprising positioning the prosthetic valve at thenative mitral annulus after the delivering step.
 10. The methodaccording to claim 9, comprising positioning the prosthetic valve sothat the lower anchoring portion anchors the frame within the nativemitral annulus by capturing tissue at a ventricular side of the nativemitral annulus when the frame is expanded.
 11. The method according toclaim 10, comprising positioning the prosthetic valve so that the upperanchoring portion anchors the frame within the native mitral annulus bycontacting tissue at the atrial side of the native mitral annulus whenthe frame is expanded.
 12. The method according to claim 10, wherein thelower anchoring portion anchors the frame within the native mitralannulus by capturing tissue of a subvalvular portion of the nativemitral valve on the ventricular side of the native mitral annulus. 13.The method according to claim 10, wherein the lower anchoring portionanchors the frame within the mitral annulus by capturing native leafletsof the native mitral valve.
 14. The method according to claim 1, whereinthe atrial portion extends radially outward from an atrial end of themain body.
 15. The method according to claim 1, wherein each strut has afirst end that is attached to the main body and a second end that isspaced from the first end.
 16. A method for implanting a prostheticvalve at a mitral valve region of a heart, the mitral valve regionhaving a native mitral annulus, the method comprising: delivering to thenative mitral annulus a prosthetic valve comprising: a frame having anexpanded and a collapsed state, the frame having a longitudinal axis andcomprising: a main body having an atrial end and a ventricular end, themain body defining inner and outer surfaces; a lower anchoring portionat the ventricular end of the main body that comprises a plurality ofanchors, each of the anchors having a first end that is attached to themain body and a second end that is spaced from the first end; and anupper anchoring portion at the atrial end of the main body thatcomprises an atrial portion configured to be positioned on an atrialside of the native mitral annulus, the atrial portion comprising aplurality of struts, the atrial portion having a first end that isattached to the main body and a second end that is spaced from the firstend; and a valve structure attached to the inner surface of the mainbody of the frame; wherein when the frame is in the collapsed state, theupper and lower anchoring portions are oriented substantially along thelongitudinal axis of the frame; wherein when the frame transitions fromthe collapsed state to the expanded state, the lower anchoring portiontransitions to a configuration having a different orientation than whenthe frame is in the collapsed state; and wherein the lower anchoringportion is configured to capture tissue at the ventricular side of thenative mitral annulus between the lower anchoring portion and the outersurface of the main body as the frame transitions from the collapsedstate to the expanded state; and expanding the frame to anchor theprosthetic valve at the native mitral annulus.
 17. The method accordingto claim 16, wherein: the plurality of anchors comprise flip-up anchors;and when the frame is in the collapsed state, the flip-up anchors areoriented substantially along the longitudinal axis of the frame; andwhen the frame transitions from the collapsed state to the expandedstate, the flip-up anchors transition to a configuration having adifferent orientation than when the frame is in the collapsed state. 18.The method according to claim 17, wherein the flip-up anchors extendfrom two or more attachment points on the main body.
 19. The methodaccording to claim 17, wherein the flip-up anchors are finger-like. 20.The method according to claim 19, wherein the flip-up anchors extendfrom one attachment point on the main body.
 21. The method according toclaim 16, wherein: the plurality of anchors comprise flip-up anchors;when the frame is in the collapsed state, the flip-up anchors extends ina ventricular direction; and when the frame transitions from thecollapsed state to the expanded state, the flip-up anchors extend in anatrial direction.
 22. The method according to claim 21, wherein: whenthe frame is in the collapsed state, the flip-up anchors aresubstantially straightened; and when the frame transitions from thecollapsed state to the expanded state, the flip-up anchors spring backto a pre-formed shape.
 23. The method according to claim 16, wherein:the plurality of anchors comprise bend-up anchors having a pre-formedcurved shape; and when the frame is in the collapsed state, the bend-upanchors are oriented substantially along the longitudinal axis of theframe; and when the frame transitions from the collapsed state to theexpanded state, the bend-up anchors transitions to a configurationhaving a different orientation than when the frame is in the collapsedstate.
 24. The method according to claim 23, wherein the bend-up anchorsextends from two or more attachment points on the main body.
 25. Themethod according to claim 23, wherein the bend-up anchors arefinger-like.
 26. The method according to claim 25, wherein the bend-upanchors each extend from one attachment point on the main body.
 27. Themethod according to claim 16, wherein: the plurality of anchors comprisebend-up anchors having a pre-formed curved shape; when the frame is inthe collapsed state, the bend-up anchors extend in a ventriculardirection; and when the frame transitions from the collapsed state tothe expanded state, the bend-up anchors extend in an atrial direction.28. The method according to claim 27, wherein: when the frame is in thecollapsed state, the bend-up anchors are substantially straightened; andwhen the frame transitions from the collapsed state to the expandedstate, the bend-up anchors spring back to the pre-formed curved shape.29. The method according to claim 16, wherein the prosthetic valve isdelivered to the native mitral annulus via a delivery sheath.
 30. Themethod according to claim 16, wherein the prosthetic valve is deliveredto the implantation site transatrially, transapically, or via thepatient's vasculature.
 31. The method according to claim 16, furthercomprising positioning the prosthetic valve at the native mitral annulusafter the delivering step.
 32. The method according to claim 31,comprising positioning the prosthetic valve so that the lower anchoringportion anchors the frame within the native mitral annulus by capturingtissue at a ventricular side of the native mitral annulus when the frameis expanded.
 33. The method according to claim 32, comprisingpositioning the prosthetic valve so that the upper anchoring portionanchors the frame within the native mitral annulus by contacting tissueat the atrial side of the native mitral annulus when the frame isexpanded.
 34. The method according to claim 32, wherein the loweranchoring portion anchors the frame within the native mitral annulus bycapturing tissue of a subvalvular portion of the native mitral valve onthe ventricular side of the native mitral annulus.
 35. The methodaccording to claim 32, wherein the lower anchoring portion anchors theframe within the mitral annulus by capturing native leaflets of thenative mitral valve.
 36. The method according to claim 16, wherein theatrial portion extends radially outward from an atrial end of the mainbody.
 37. The method according to claim 16, wherein each strut has afirst end that is attached to the main body and a second end that isspaced from the first end.
 38. A method for replacing a damaged ordiseased mitral valve in a subject comprising: delivering to the mitralvalve annulus of said subject a valve prosthesis that comprises a stenthaving an expanded and an unexpanded state and that includes a longaxis; a middle region having first and second ends and comprising aframework that defines inner and outer surfaces; a lower flange portionat the first end of the middle region that comprises a plurality offlange elements, each of said elements having a first end that isattached to the middle region and an opposed second end that is spacedfrom the first end; and, an upper flange portion at the second end ofthe middle region that comprises a plurality of flange elements, each ofsaid elements having a first end that is attached to the middle regionand an opposed second end that is spaced from the first end; and, avalve that is attached to the inner surface of the middle region of thestent, wherein, when said stent is in the unexpanded state, the upperand lower flange portions are oriented substantially along the long axisof the stent; when said stent transitions from the unexpanded state tothe expanded state, the lower flange portion transitions in space sothat it is no longer oriented substantially along the long axis of thestent; and, the lower flange portion grasps tissue at the ventricularside of the annulus by enfolding it between the lower flange portion andthe outer surface of the middle region as the stent transitions from theunexpanded state to the expanded state and, expanding said stent toanchor the prosthesis at the mitral valve annulus.
 39. The methodaccording to claim 38 wherein the valve prosthesis is delivered to theimplantation site by a positioning catheter.
 40. The method according toclaim 38 wherein the valve prosthesis is delivered to the implantationsite transatrially, transapically, or percutaneously.
 41. The methodaccording to claim 38 further comprising positioning said valveprosthesis at the implantation site after said delivering step.
 42. Themethod according to claim 41 comprising positioning said valveprosthesis so that the lower flange portion anchors the stent within themitral annulus by grasping tissue at the ventricular side of the annuluswhen said stent is expanded.
 43. The method according to claim 42comprising positioning said valve prosthesis so that the upper flangeportion anchors the stent within the mitral annulus by grasping tissueat the atrial side of the annulus when said stent is expanded.
 44. Themethod according to claim 42 wherein the lower flange portion anchorsthe stent within the mitral annulus by grasping the subvalvularapparatus at the ventricular side of the annulus.
 45. The methodaccording to claim 42 wherein the lower flange portion anchors the stentwithin the mitral annulus by grasping leaflets of the native mitralvalve.